Neuro Cards

A 60-year-old male presents via ambulance to the emergency department with new onset seizure. His wife, who accompanies him, states that he has been complaining of a headache and pressure behind his eyes for the past 3 days. He complained of being "ice-cold" this morning, despite appearing diaphoretic and feeling hot. Two hours prior to the seizure he was confused and "acting funny". The patient is post-ictal and unable to provide any further history. Past medical history reveals ankylosing spondylitis being treated with a TNF-α inhibitor after failing NSAIDS. Vital signs reveal a temperature of 102.7 F (39.3), a blood pressure of 98/60 mmHg, a heart rate of 112/min and an oxygen saturation of 98% on room air. Physical examination reveals healing sores on his lips. Laboratory reveals a WBC of 12.8 x 103/mcL (reference range: 4.8-10.8 x 103/mcL). A contrasted topography scan of his brain is normal, with subsequent lumbar puncture revealing grossly bloody cerebral spinal fluid which is sent for analysis. Magnetic resonance imaging is ordered as shown in the exhibit. *The medication most likely to give him the best survival benefit is* A. acyclovir B. amphotericin C. ceftriaxone D. glucocorticoids E. pyrimethamine and sulfasalazine

*acyclovir* This patient has symptoms and signs of herpes simplex virus (HSV) encephalitis, a viral infection characteristically affecting the temporal lobe, as seen in the exhibit. Clinical manifestations include altered mental status, confusion, fever, headaches, and seizures. The treatment of choice for HSV encephalitis is acyclovir, which if given at the first suspicion of the disease reduces the risk of mortality significantly. HSV-1 is the most common subtype of HSV encephalitis and is thought to occur from an oral HSV primary infection or reactivation. Those on immunosuppression medications including TNF-α inhibitors are at an increased risk. HSV DNA polymerase chain reaction (PCR) of the cerebral spinal fluid is considered the gold standard to diagnose HSV encephalitis. However, this test takes time to process, and therefore other adjunctive tests may assist in the diagnosis, as discussed below: 1. Lumbar puncture: Cerebral spinal fluid would display lymphocytic pleocytosis, an increased number of erythrocytes, and elevated protein with normal glucose levels. An impressive amount of red blood cells may be seen, which is caused from temporal lobe necrosis. 2. MRI: Temporal lobe necrosis, often unilateral, in the setting of seizures and fevers is consistent with HSV encephalitis. CT scan is often normal. 3. Electroencephalogram (EEG): Periodic lateralizing epileptiform discharges is characteristic. Even in the setting of early and aggressive antiviral therapy, HSV encephalitis carries a high mortality rate. Approximately 25% will die from the disease despite treatment, while two-thirds of survivors will be left with significant neurologic deficits. For this reason, it is imperative to begin empiric intravenous acyclovir when the disease is being considered, and not waiting for confirmatory testing.

A 44-year-old male presents to his primary care physician with complaint of new onset fasiculations in his quadriceps muscles. History reveals a progressive disorder that began in the face, moved to the upper extremities, and finally moved to the lower extremities. Physical examination reveals spasticity in elbow flexion bilaterally, fasciculations of his biceps muscles and tongue, as well as dysarthria, and clonus of his ankle reflexes. The new onset of fasciculations most likely indicates degeneration in which of the following locations? A. anterior horn B. lateral horn C. posterior horn D. primary motor cortex E. reticular formation

*anterior horn* Although no test can provide a definitive diagnosis of amyotrophic lateral sclerosis (ALS), the presence of upper motor neuron (UMN) and lower motor neuron (LMN) signs in the same limb or limbs is strongly suggestive. UMN signs include spasticity and clonus, while LMN signs include fasciculations. ALS can cause demyelination in the anterior horn of the spinal cord and the motor areas of the cortex and brainstem. This patient has dysarthria (UMN, cortex), fasciculations in his tongue (LMN, brainstem), spasticity with elbow flexion (UMN, cervical), fasciculations in his biceps muscles (LMN, cervical), and clonus of his ankle reflexes (UMN, lumbosacral). ALS fits the signs and symptoms in this patient. Since the LMN cell bodies to the quadriceps muscles are located in the anterior horn of the spinal cord, this is the part of the nervous system that has degenerated to cause this patient's new symptoms, fasciculations in his quadriceps muscles (LMN, lumbosacral). Answer B: The lateral horns of the spinal cord contain the preganglionic sympathetic neurons of the autonomic nervous system at spinal cord levels T1-L2, but do not contain LMNs that innervate the quadriceps muscles. Answer C: The posterior horns of the spinal cord contain the second order neurons for somatic and visceral pain pathways, but do not contain LMNs that innervate the quadriceps muscles. Answer D: The primary motor cortex contains UMNs of the somatic nervous system, but does not contain LMNs that innervate the quadriceps muscles. Both UMNs and LMNs for multiple body segments degenerate with ALS. Answer E: The reticular formation regulates consciousness and arousal but does not contain any UMNs or LMNs of the somatic nervous system. *Bottom Line*: Amyotrophic lateral sclerosis is a demyelinating disease that can affect the anterior horn of the spinal cord and the motor areas of the cortex and brainstem. It manifests with upper motor neuron and lower motor neuron signs and symptoms in the same limb or limbs, although no test can provide a definitive diagnosis.

A 32-year-old male with a history of asthma presents to the physician's office after experiencing a fall the previous day. He states that his "legs just were not working right." He is concerned because he has had several of these episodes over the last year, with increasing frequency over the last several months. Further history reveals that his father experienced similar symptoms before dying in a car accident in his early thirties, whereas his mother, 39-year-old sister, and 35-year-old brother are asymptomatic. The physician performs a thorough neurological examination and discovers the findings demonstrated in the video. Genetic testing reveals an abnormality located on chromosome 6p. Based on the information provided, which foundational genetic principle best explains this patient's illness? A. anticipation B. autosomal dominant C. autosomal recessive D. Y-linked inheritance E. X-linked inheritance

*autosomal dominant* This patient's presentation is consistent with spinocerebellar ataxia (SCA), a heterogeneous group of mostly autosomal dominant neurologic disorders that present with varying degrees and forms of cerebellar dysfunction. Most likely among these disorders is SCA type 1 (SCA1), which typically presents in the third to fourth decade of life, although there is variability in onset and clinical severity. It is characterized clinically by progressive cerebellar ataxia, dysarthria, and bulbar dysfunction. As the disease progresses, the patient may experience muscle wasting and dystonic symptoms. However, the phenotypic manifestations of SCA1 are not specific and no formal diagnostic criteria exist. Rather, the diagnosis of SCA1 rests on molecular genetic testing to differentiate it from other neurologic disorders presenting with ataxia. The genetic test detects an abnormal CAG trinucleotide expansion in ATXN1 on chromosome 6p and is inherited in an autosomal dominant fashion. Affected individuals have alleles with 39 or more CAG trinucleotide repeats that leads to the production of an abnormal protein, ataxin-1 causing the patient's symptoms. SCA1 is inherited in an autosomal dominant manner. Offspring of an affected individual have a 50% chance of inheriting the expanded allele. Figure illustrates a simple pedigree of autosomal dominant inheritance, in which case an abnormal gene from one parent can cause disease. A parent with an autosomal dominant condition has a 50% chance of having a child with the condition. This is true for each pregnancy. Physical examination of this patient reveals dysmetria; notice that the patient initially moves his finger in the wrong direction, then corrects halfway to the target. This finding is nonspecific but is a sign of cerebellar dysfunction. Other physical exam findings indicative of cerebellar dysfunction include dysarthria (difficulty modulating speech pitch or volume), dysdiadochokinesia (impaired rapid alternating hand movements), intention tremor and gait abnormalities. Answer A: Anticipation is a genetic term that describes a mutation exhibiting stronger phenotypic expression with each subsequent generation. Moreover, anticipation is typically found in disorders involving repeated three-nucleotide sequences that expand with repeated replications, such as spinocerebellar ataxia type 1 (SCA1) that is the most likely diagnosis of this patient. However, this patient is experiencing similar symptoms as his mother at approximately the same age, so anticipation is not likely a factor in this case. The classic example of anticipation is Huntington's disease, which results from the expansion of a CAG-repeat sequence on chromosome 4p and demonstrates more severe symptoms and an earlier age of onset in each subsequent generation. Figure illustrates how repeating CAG trinucleotide expansions can result in the addition of glutamine residues in a protein, such as the huntington and ataxin proteins. Answer C: There are many autosomal recessive disorders that cause ataxia or dysmetria, including Friedrich's ataxia, Gillespie Syndrome and Dandy-Walker syndrome. However, these and most other autosomal recessive disorders will present at birth or in childhood, will have more severe symptoms, and may be associated with other prominent neurologic or developmental symptoms. This patient's presentation is more consistent with autosomal dominant inheritance generally, and with spinocerebellar ataxia specifically, given the genetic locus. Answer D: Y-linked inheritance is easily recognized because it manifests as exclusive transmission from father to son; all affected individuals are male. However, although several forms of male sexual dysfunction have been linked to variants on the Y chromosome, there are no confirmed examples of other types of Y-linked diseases. This patient's presentation is most consistent with spinocerebellar ataxia (SCA), a heterogeneous group of mostly autosomal dominant neurologic disorders that present with varying degrees and forms of cerebellar dysfunction. Answer E: There are several forms of ataxia that are caused by x-linked inheritance, including X-linked cerebellar hypoplasia and pyruvate dehydrogenase deficiency. However, these and other X-linked disorders present similarly to autosomal recessive disorders, demonstrating earlier onset and more severe symptoms and comorbidities. Moreover, the patient appears to have inherited this disorder from his mother; since X-linked disorders are uncommon in females, the gene responsible is more likely autosomal. *Bottom Line*: Spinocerebellar ataxia is a heterogeneous group of autosomal dominant neurologic disorders that present with ataxia. Physical examination may reveal signs of cerebellar dysfunction, including dysmetria. COMBANK Insight : There are two approaches to genetic disorders. One is to memorize every disorder and its genetic properties; the other is to look at the patient presentation for clues. Autosomal recessive disorders present earlier and with more severe symptoms, and are often found in smaller ethnic groups. Autosomal dominant disorders will either have less severe symptoms or a later age of onset, allowing the disease to be passed on to subsequent generations. X-linked disorders are predominantly found in males, and are generally closer to recessive disorders in terms of their severity and age of onset. . Y-linked diseases are rare and linked to male sexual dysfunction.

A 30-year-old female presents to the emergency department with a severe headache, high fever, and altered mental status. She complains of nausea, vomiting, loss of appetite, and a seizure that caused her to finally call an ambulance. Her past medical history is unremarkable, and she reports that a week ago, she went camping on a lake with friends and took many turns jumping off of a tire swing into the water. Also, during the past 2 days, everything has been smelling "funny." Kernig and Brudzinski signs are positive and lumbar puncture reveals that the cerebrospinal fluid displays high levels of erythrocytes and white blood cells (mostly polymorphonuclear neutrophils) along with a very high opening pressure. Despite treatment, the patient rapidly declines and succumbs to the infection, which was diagnosed as A. fungal meningitis B. granulomatous amebic encephalitis C. HSV encephalitis D. neurocysticosis E. primary amebic meningoencephalitis

*primary amebic meningoencephalitis* Primary amebic meningoencephalitis (PAM) is caused by Naegleria fowleri, a protozoan that infects the nasal cavity and crosses the cribriform plate to infect the central nervous system (CNS). N fowleri is usually transmitted by diving into warm freshwater lakes and ponds, where the parasite lives in the sediment. PAM presents as a rapidly developing CNS infection similar to meningoencephalitis, but with hemorrhagic complications and severe cranial hypertension that leads to a very high mortality rate. In the early stage of infection, sense of smell may change and could reflect the invasion of the organism through the olfactory mucosa. Prognosis of PAM is poor, and amphotericin B has shown the most promise during attempted treatment regimens. Answer A: The most common fungal meningitis is caused by Cryptococcus neoformans, the primary cause of AIDS-associated meningitis. C neoformans is an encapsulated yeast that is transmitted via inhalation of contaminated bird droppings and is often visualized with an India ink stain of cerebrospinal fluid (CSF). Answer B: Granulomatous amebic encephalitis is largely caused by Acanthamoeba and Balamuthia, which are protozoan pathogens acquired through contaminated soil and a number of water environments such as sewage, brackish water, humidifiers, and contact lenses. The parasites can invade the bloodstream and spread hematogenously to the brain. This infection manifests with similar symptoms as N fowleri but usually affects immunocompromised patients and presents more gradually over weeks to months with the same prognosis. Answer C: Encephalitis caused by herpes simplex virus typically presents with fever, headache, seizures, focal neurologic defects, and impaired consciousness. This would be on one's differential, but the CSF profile would have white blood cell infiltrates that are predominantly lymphocytes, and the patient history would have likely indicate sexually transmitted infections or recurrent cold sores. Answer D: Neurocysticercosis is caused by ingestion of Taenia solium eggs. T solium is a helminth transmitted by ingesting cysticerci (infectious cysts) in undercooked pork and manifests as an adult tapeworm infection characterized by abdominal discomfort, weight loss, and diarrhea. If T solium eggs are ingested or present by auto-inoculation, the larval worms hatch in the gastrointestinal tract and then migrate throughout the body to various organs where they can form calcifications. The brain is particularly involved, which leads to development of cysticercosis with CNS symptoms that often include seizures. Bottom Line: Naegleria fowleri is a parasite that causes the highly pathogenic primary amebic meningoencephalitis and is transmitted through contaminated water that contacts the nasal mucosa.

A 14-year-old male presents to the emergency department via ambulance for evaluation of mental status changes and vomiting. Physical examination reveals a febrile patient with aphasia, and during the examination, the patient has a seizure. History indicates that the patient is attending a summer camp on a lake in Ohio. Laboratory studies reveal that the etiology is an enveloped virus with a negative sense, circular, single-stranded RNA genome in 3 segments. The most likely diagnosis is A. Eastern equine encephalitis B. La Crosse encephalitis C. St. Louis encephalitis D. West Nile encephalitis E. Western equine encephalitis

*La Crosse encephalitis* La Crosse virus is a member of the Bunyaviridae family and is the most common and most pathogenic of the California encephalitis serogroup of bunyaviruses. These viruses are enveloped with a negative sense, circular, single-stranded RNA genome with helical nucleocapsids and are transmitted through the bite of the Aedes triseriatus mosquito and have rodent reservoirs in nature. The virus is most prevalent in the Southeastern and Midwestern US (see map). This disease begins with a prodromal phase, lasting 1-4 days, consisting of fever, chills, nausea, vomiting, headache, and abdominal pain. This is followed by fever, somnolence, and mental status change or obtundation. Physical findings include focal neurologic deficits, such as aphasia, incoordination, focal motor abnormalities, and paralysis. Diagnosis is made by clinical history, virus isolation, or detecting specific IgM in cerebrospinal fluid samples. Supportive care is the mainstay treatment and ribavirin has been used but with unproven efficacy. Most patients with clinical symptoms recover completely. However, 20% of patients develop behavioral problems or recurrent seizures. Mortality rates are < 1%. The other serogroup of medically relevant bunyaviruses is hantavirus, which is transmitted by exposure to rodent excrement and cause a severe pulmonary infection with mortality rates near 50%. Answer A: Eastern equine encephalitis is caused by an alphavirus genus member of the Togaviridae family. These viruses are enveloped with a positive sense, linear, single-stranded RNA genome with icosahedral nucleocapsids. The virus is transmitted by the Culiseta melanura mosquito. The disease primarily occurs in the Eastern United States and would be on one's differential, but the biology of the virus does not fit the laboratory findings. Answer C: St Louis encephalitis is caused by the St Louis encephalitis virus, a member of the Flaviviridae family. These viruses are enveloped with a positive sense, linear, single-stranded RNA genome with icosahedral nucleocapsids. The virus is transmitted by a mosquito of the Culex genus and would be on one's differential, but the biology of the virus does not fit the laboratory findings. Answer D: West Nile encephalitis is caused by the West Nile virus, a member of the Flaviviridae family. These viruses are enveloped with a positive sense, linear single-stranded RNA genome with icosahedral nucleocapsids. The virus is transmitted by the Culex, Aedes, and Anopheles mosquitoes. West Nile virus would also be on one's differential and has been reported throughout most of the United States, with foci of infection in the Northeastern and South Central United States. Again, the biology of the virus does not fit the laboratory findings. Answer E: Western equine encephalitis is caused by an alphavirus genus member of the Togaviridae family. These viruses are enveloped with a positive sense, linear, single-stranded RNA genome with icosahedral nucleocapsids. Western equine encephalitis is transmitted by the mosquitos of the Culex and Culiseta genera. It would be on one's differential as the disease primarily occurs in the Midwestern and Western United States, but the biology of the virus does not fit the laboratory findings. *Bottom Line*: The La Crosse virus, a mosquito-transmitted member of the Bunyaviridae family, causes encephalitis characterized by mental status change, neurologic defects, and fever.

A 23-year-old male presents to the emergency department with complaints of right knee pain and an inability to walk. The patient was playing baseball when he suddenly heard a popping noise in his knee after sliding into third base. Physical examination is negative for joint line tenderness. When the patient is asked to lie supine with the hips flexed at 45º and the knees flexed to 90º, the tibial tubercles seem to lie more posterior on the right leg than the left. When the patient then contracts the right quadriceps muscle against resistance, the tibia moves back into normal position. *Which of the following structures is most likely damaged?* A. ACL B. MCL C. medial meniscus D. patellar tendon E. PCL

*PCL* The test described is called the quadriceps activation test. It tests for posterior cruciate ligament (PCL) tears. The PCL primarily prevents posterior translation of the tibia on the femur. When the PCL is ruptured, there is no support to posterior translation; therefore, the tibia rests in a more posterior position than usual. When the quadriceps muscles are tightened from a supine position against resistance, the tibia will translate anteriorly into normal position. This is due to the quadricep muscles' insertion onto the tibia, which causes the extension of the leg and anterior movement of the tibia. PCL tears most commonly occur when the leg is in flexion because the PCL is under most stress when the leg is in flexion. Thus, PCL tears commonly occur in baseball players when they are sliding into a base due to the excess flexion that occurs. The figure shows the posterior view of the connective tissue structures of the knee joint. The PCL prevents posterior translation of the tibia on the femur and attaches the medial condyle of the femur to the posterior intercondylar tibia.

A 15-year-old male presents to a neurologist with a complaint of difficulty looking up. History reveals progressive onset beginning about one month earlier. Physical examination reveals paralysis of conjugate vertical gaze with convergence-retraction nystagmus when attempting vertical gaze. Ocular examination reveals loss of pupillary light reflex with penlight directed at either eye and no change in either pupil with the swinging-flashlight test. However, pupils constrict in response to redirecting gaze from a distant target to a near target. Superior eyelid retraction is also present for both eyes. *What is the most likely diagnosis?* A. Adie syndrome B. Argyll-Robinson pupil C. Horner syndrome D. Marcus Gunn pupil E. Parinaud syndrome

*Parinaud syndrome* Parinaud syndrome (dorsal midbrain syndrome) includes impaired vertical gaze, normal to large pupils, light-near dissociation, convergence-retraction nystagmus, and eyelid retraction (Collier's sign). It can be caused by pineal gland tumor (especially in the young), hydrocephalus (due to dilation of suprapineal recess), multiple sclerosis, and brainstem infarction. The pineal gland tumor impairs vertical gaze by compressing the vertical gaze centers and their pathways in the superior midbrain tectum, and sometimes the superior colliculi. Convergence-retraction nystagmus with attempted vertical gaze can accompany the loss of vertical gaze. The loss of the pupillary light reflex but retention of the near response when redirecting gaze from a distant target to a near target occurs because the pretectal nuclei or the posterior commissure connection between them is affected while the oculomotor nuclei or nerve and supraoculomotor area are spared. This causes pupils to constrict much less in response to light than to accommodation, called light-near dissociation. Collier's sign is also due to damage to the posterior commissure, specifically neurons involved in inhibiting contraction of levator palpebrae superioris. Without tonic inhibition of that muscle the eyelid retracts and elevates. Some of the key structures in rostral midbrain that can be affected with Parinaud syndrome. Answer A: Adie syndrome presents with tonic dilated pupil, no pupillary light reflex, and slow prolonged response with attempted near vision. Diseases of the ciliary ganglion cause Adie syndrome, with lesion of the parasympathetic postganglionic neurons of the ciliary ganglion responsible for the clinical signs. The light-near dissociation occurs because the ciliary ganglion has 20X as many neurons projecting to the ciliary muscle as to the pupillary sphincter muscle, thus some sparing of the near response of accommodation. This idiopathic neuropathy increases in frequency with middle age, and selectively affects ciliary ganglion and spinal cord neurons for deep tendon reflexes. Thus decreased deep tendon reflexes can accompany the loss of the pupillary light reflex. There is no loss of vertical gaze. Answer B: Argyll-Robertson pupils are bilateral small pupils that accommodate for near vision but lack the pupillary light reflex. It is caused by neurosyphilis or diabetic neuropathy that affects the pretectal area but not the oculomotor nuclei or supraoculomotor area, so light-near dissociation occurs. There is no loss of vertical gaze. Answer C: Horner syndrome presents with pupil constriction (miosis), ptosis (tarsal muscle), and anhydrosis. It occurs with damage to the hypothalamospinal tract in the brainstem or the sympathetic pathway from the spinal cord to targets in the head and neck. The affected eye has reduced constriction with the pupillary light reflex because the pupil is already partially constricted. There is no loss of vertical gaze. Answer D: Marcus Gunn pupil (relative afferent pupillary defect) has slower or reduced pupil constriction coupled with diminished near response of accommodation. Marcus Gunn pupil occurs with diseases of the retina or optic nerve that affect the afferent limb of both the pupillary light reflex and accommodation. Swinging flashlight (alternating light) test shows normal constriction for the normal eye alternating with slower and reduced constriction for the diseased eye, which looks like dilation. Hence, the swinging flashlight test appears to show alternating constriction and dilation as the penlight is directed back and forth. There is no loss of vertical gaze. *Bottom Line*: Parinaud syndrome (dorsal midbrain syndrome) pairs impaired vertical gaze with light-near dissociation.

A 44-year-old female presents to an outpatient clinic with a complaint of double vision and headache. History reveals these symptoms began the day before. Eye examination reveals horizontal gaze palsy for the right eye with gaze to the left, as shown in the exhibit. However, forward-directed gaze is normal, gaze to the right is normal, convergence for near vision is normal, and pupillary light reflexes have normal direct and consensual responses with a penlight directed to either eye. Which of the following is the most likely lesion site? A. L medial longitudinal fasciculus B. L paramedian pontine reticular formation C. R medial longitudinal fasciculus D. R oculomotor n. E. R paramedian pontine reticular formation

*R medial longitudinal fasciculus* The eye examination suggests a lesion of the right medial longitudinal fasciculus (MLF). This is because the patient can not adduct the right eye, but does have normal near vision convergence and normal pupillary light reflexes showing that the oculomotor nerve and nucleus are undamaged. This condition is called internuclear ophthalmoplegia (INO). Bilateral INO is correlated with multiple sclerosis. The neural pathway for horizontal gaze to the left includes the right frontal eye field, left paramedian pontine reticular formation, left abducens nucleus, right MLF, and right oculomotor nucleus. The left abducens nerve innervates the left lateral rectus muscle, and the right oculomotor nerve innervates the right medial rectus muscle, with activation of both muscles necessary for horizontal gaze to the left. The right MLF coordinates the right oculomotor nucleus with the left abducens nucleus for gaze to the left, and the left MLF coordinates the left oculomotor nucleus with the right abducens nucleus for gaze to the right. Answer A: If the left MLF was the lesion site, the patient would have horizontal gaze palsy for the left eye, with gaze to the right due to loss of adduction for the left eye. Answer B: If the left paramedian pontine reticular formation was the lesion site, the patient would have left horizontal gaze palsy for both eyes rather than horizontal gaze palsy for the right eye with gaze to the left. Answer D: If the right oculomotor nucleus was the lesion site, the patient would not only have horizontal gaze palsy for the right eye with gaze to the left, but would also lose convergence for near vision, and would have a lateral strabismus of the right eye rather than normal forward directed gaze. Answer E: If the right paramedian pontine reticular formation was the lesion site, the patient would have right horizontal gaze palsy for both eyes rather than normal gaze to the right. Bottom Line: Internuclear ophthalmoplegia (INO) occurs from a lesion in the medial longitudinal fasciculus, which coordinates the ipsilateral oculomotor nucleus with the contralateral abducens nucleus for horizontal eye movements.

A 65-year-old female presents to the emergency department with complaints of fever and malaise. History reveals a sudden onset of fever the day prior, which she tried to treat with over-the-counter cold medication while maintaining normal daily routine, including meals. Urine output and bowel movements have been normal. Physical examination reveals vital signs in the normal range except for a body temperature of 41°C (105.8°F). CT scan reveals an intraparenchymal bleed in the hypothalamus. *Which of the following hypothalamic nuclei is most likely affected?* A. anterior B. dorsomedial C. lateral D. supraoptic E. ventromedial

*anterior* The hypothalamus influences responses to both internal and external conditions, especially visceral functions and emotional behavior. Its primary role is maintenance of homeostasis through regulation of numerous functions, including feeding and drinking behavior, temperature, blood pressure, arousal, and wakefulness. The hypothalamus is part of the diencephalon and located below the third ventricle and above the optic chiasm and pituitary gland. The hypothalamus can be divided into different areas, zones, or nuclei, with different functions. The anterior nucleus of the hypothalamus contributes to regulation of body temperature (thermoregulation). It is under parasympathetic control and is responsible for cooling the body through stimulation of panting or sweating. Thus, a lesion in the anterior nucleus of the hypothalamus causes difficulty lowering core body temperature. Answer B: The dorsomedial nucleus of the hypothalamus contributes to emotional behavior. Stimulation causes sham rage. Lesion causes decreased aggression and decreased feeding. Answer C: The lateral nucleus of the hypothalamus contributes to feeding responses. Stimulation causes increased feeding. Lesion causes decreased feeding. Answer D: The supraoptic nucleus of the hypothalamus produces oxytocin and antidiuretic hormone for transport to the circulatory system. Stimulation causes increased blood volume, blood pressure, and metabolism. Lesion causes diabetes insipidus. Answer E: The ventromedial nucleus of the hypothalamus contributes to feeding responses. Stimulation causes decreased feeding. Lesion causes increased feeding.

A 9-year-old boy presents to his pediatrician with right knee pain. The patient has had an intermittent limp for the past two weeks which becomes progressively worse after exertion. He has also been complaining of intermittent hip pain of the same side. Physical examination reveals a patient with a BMI of 17 kg/m2, which puts him in the 75th percentile for his age. He can bear weight on exam. He has decreased range of motion in the right hip. The patellar grind test is negative, and there is no pain with palpation to his hip or knee. Osteopathic examination reveals a tenderpoint 7 cm medial to the ASIS on the right. *The most likely diagnosis in this patient is:* A. avascular necrosis of the femoral head B. Chondromalacia C. Osgood-Schlatter disease D. septic arthritis E. slipped capital femoral epiphysis

*avascular necrosis of the femoral head* Avascular necrosis of the femoral head, also known as Legg-Calve-Perthes disease, is due to an interruption of adequate blood flow to the femoral head. It most commonly affects boys aged 3 to 12-years-old and can present with hip pain and a limp of either acute or insidious onset. Pain in the knee occurs due to referred pain from the obturator nerve. A physical examination will reveal a decreased range of motion of the hip. The patient is able to bear weight, and pain becomes progressively worse after exertion. Plain film radiographs may be normal, but when abnormal they will show collapse of the femoral head which causes the femoral head to appear flattened and widened. Bone scans will show decreased perfusion to the femoral head. A tenderpoint noted 7 cm medial to the ASIS on the right represents dysfunction of the iliacus muscle, which attaches to the lesser trochanter of the femur, and would perhaps demonstrate dysfunction in a patient with abnormal hip mechanics. Answer B: Chondromalacia is softening of articular cartilage of the patella that may eventually lead to patellofemoral arthritis. Chondromalacia is common in women due to weakness of the vastus medialis oblique muscle, which results in increased lateral subluxation of the patella. Patients present with anterior knee pain that is worse upon climbing stairs. Patients will have a positive patellar grind test. Answer C: Osgood-Schlatter disease is an overuse injury that is most common in physically active boys aged 10 to 15-years-old. It results from increased traction at the insertion of the patellar tendon into the tibial tuberosity from repetitive quadriceps contraction. Patients present with pain and swelling over the tibial tubercle after repetitive activities such as running or jumping. Pain is elicited with palpation at the site of the insertion of the patellar tendon. Answer D: Pediatric septic arthritis of the hip results from direct inoculation from the external environment or through hematogenous spread of an infection such as osteomyelitis. Patients will present with the inability to bear weight on the affected side, fever, elevated white blood cell count, and an elevated erythrocyte sedimentation rate. The child will hold his hip in flexion, abduction, and external rotation which decreases the pain. This must be treated quickly and aggressively, as failure to do so can result in joint destruction and long-term morbidity. Answer E: Slipped capital femoral epiphysis most commonly affects overweight or obese African-American boys between the ages of 10 to 16-years-old. It occurs when the femoral epiphysis slips posteriorly which results in a limp of insidious onset, impaired internal rotation, anterior hip or knee pain. Plain film radiographs will reveal the abnormality. This lesion can cause a similar presentation to Legg-Calve-Perthes disease; however, it can be ruled out due to epidemiological factors such as the wrong age group and the presence of a normal BMI. *Bottom Line*: Legg-Calvé-Perthes disease most commonly presents in children 3 to 12-years old. They typically present with hip pain and a limp of either acute or insidious onset as well as mild pain in the anterior thigh or knee.

An 18-year-old Hispanic male presents to the clinic for fever and joint pain of three weeks' duration. He states that his fever seems to rise and fall throughout the day and he often sweats at night. He has generalized joint pain, but it is most pronounced in the sacroiliac joints. Physical examination reveals the presence of a physiologic heart murmur previously documented. He recently returned from Mexico where he was working on his uncle's dairy farm producing goat cheese and unpasteurized milk. Which of the following is the most likely diagnosis? A. brucellosis B. Chagas Dz C. infective endocarditis D. leptospirosis E. tularemia

*brucellosis* Brucellosis, caused by Brucella spp, is a common zoonotic infection transmitted to humans from many different animals including goats, sheep, camels, cows, etc. In this case, the most likely organism is Brucella melitensis, which is acquired from contact with infected goats and sheep. Direct contact with fluids from infected animals via disrupted skin or mucous membranes, inhalation of infectious aerosols, conjunctival inoculation, or from ingestion of contaminated food products, such as unpasteurized milk or cheese, are the common modes of transmission. Brucella spp are small gram-negative aerobic coccobacilli that have the unique ability to invade both phagocytic and nonphagocytic cells and surviving by suppressing the bactericidal responses of the immune system. Brucellosis presents with a varying degree of symptoms, but the most common is an undulating fever that rises and falls in degree during the disease. Other common features of the disease include joint pain, most commonly the sacroiliac joint and large joints of the lower extremities and profuse sweating. Answer B: Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. It is prevalent in South America, but also in the southwestern United States. T. cruzi is most commonly found in the reduviid bug, also referred to as the kissing bug, and is transmitted to humans through the blood-sucking insect. Cardiomyopathy and gastrointestinal disease are the major manifestations of Chagas disease. Although the patient does have a heart murmur, it was classified as physiologic and long-standing and should not be of concern. Answer C: Infective endocarditis, most commonly caused by Staphylococcus aureus, is an infection of the endocardium and/or heart valves that involve the formation of vegetations. Low-grade fever and arthralgias are common features of the disease. Although this patient does have a fever with a heart murmur, the murmur is considered pathophysiologic or "innocent" and should not raise a further concern of infective endocarditis. Answer D: Leptospirosis, a disease cause by the spirochete Leptospira interrogans, has recently been recognized as a re-emerging infectious disease among humans and animals. Human leptospirosis is often required by coming in contact with animal urine either directly or indirectly. Leptospira are thin, coiled, gram-negative, motile aerobic organisms with hooks that enable them to burrow into tissue. An acute illness follows exposure to Leptospira usually manifesting as fever, rigors, sudden headaches, nausea and vomiting, anorexia, diarrhea, cough, pharyngitis, nonpruritic skin rash, and muscle pain. Answer E: Tularemia is caused by Francisella tularensis, a gram-negative pleomorphic bacterium. F.tularensis is found worldwide in many animal species. The presentation of tularemia, although variable based on the route of transmission, shares the development of an acute febrile illness, tender hepatosplenomegaly, myalgias, and malaise after an exposure to the infected host within an average of 3 to 4 days. In the most common form, the ulceroglandular form, an ulcer will be present at the site of entry. Although numerous animals carry the bacteria, rabbits and ticks most commonly are implicated in human cases. Bottom Line: Brucellosis is transmitted through direct contact with infectious animal fluids or the ingestion of unpasteurized milk or cheese. It commonly presents with undulating fever, profuse sweating, and joint pain.

An 18-year-old male presents to the emergency department with the complaint of paralysis of muscles on the right side of his face. History reveals that this weakness began approximately 2 weeks ago and has progressively worsened. In conjunction with the facial weakness, he had a circular rash on his back 2 weeks ago that disappeared after 1 week. The facial weakness and circular rash both began while on a camping trip. Physical examination reveals that he cannot blink his right eye, raise his right eyebrow, or seal his lips on the right side. *For the clinical signs present, the relevant nucleus of the affected cranial nerve is located in which region of the brainstem?* A. caudal midbrain near the cerebral aqueduct B. caudal pons near the fourth ventricle C. mid pons near the forth ventricle D. rostral medulla near the forth ventricle E. rostral midbrain near the cerebral aqueduct

*caudal pons near the fourth ventricle* This patient has *Bell palsy*, which is an often temporary paralysis of the facial nerve (cranial nerve [CN] VII). This can occur as an isolated disorder, sometimes in conjunction with a herpesvirus infection, or it can occur as a component of a systemic disease. The latter is true in this case, as the circular rash refers to the erythema migrans associated with the early stage of Lyme disease. The facial nerve innervates muscles of facial expression, including those that supply the eyelids, forehead, lips, and cheeks with lower motor neurons from the facial motor nucleus. This nucleus is *located in the caudal pons near the fourth ventricle*. The lower motor neuron axons from this nucleus loop around the abducens nucleus then exit the caudal pons anterolaterally as part of the facial nerve. Answer A: The trochlear nucleus (CN IV) is located in the caudal midbrain near the cerebral aqueduct. The lower motor neuron axons decussate (cross midline) inside the brainstem before exiting posteriorly. The trochlear nerve provides innervation solely to the superior oblique muscle of the eye. Damage to the left trochlear nucleus would result in the right eye looking upward with a leftward horizontal gaze but would not affect the muscles of facial expression. Answer C: There are 3 nuclei associated with the trigeminal nerve (CN V) located in the mid pons near the fourth ventricle. Lower motor neurons of the trigeminal motor nucleus have axons that exit the brainstem laterally to innervate muscles of mastication. Damage to the trigeminal motor nucleus would result in jaw deviation but would not affect the muscles of facial expression. Also, the principal sensory nucleus and mesencephalic nucleus of CN V are in this same region. They are responsible for tactile sensation and proprioception from the face. Damage to these 2 nuclei would result in a loss of tactile sensation and proprioception for the face but would not affect the muscles of facial expression. Answer D: The hypoglossal nucleus (CN XII) is located in the rostral medulla near the fourth ventricle. Lower motor neurons of the hypoglossal nucleus have axons that exit the brainstem anterolaterally to innervate most of the tongue muscles. Damage to the hypoglossal nucleus would result in ipsilateral atrophy of the musculature of the tongue and cause ipsilateral deviation of the tongue when protruded but would not affect the muscles of facial expression. Answer E: The oculomotor nucleus (CN III) is located in the rostral midbrain near the cerebral aqueduct. Lower motor neurons of the oculomotor nucleus have axons that exit the brainstem anteromedially as part of the oculomotor nerve to innervate 4 extraocular eye muscles and the levator palpebrae superioris muscle. Damage to the oculomotor nucleus would result in lateral strabismus and ptosis but would not affect the muscles of facial expression. *Bottom Line*: The facial nerve is responsible for innervating the muscles of facial expression. Its nucleus is found in the caudal pons near the fourth ventricle.

A 72-year-old male presents to his primary care physician with a complaint of his hand shaking whenever he tries to write down his grocery list. This began 3 weeks earlier and has become more pronounced in recent days. History reveals he has multiple sclerosis. On admission he has blood pressure of 108/70 mmHg, heart rate of 84/min, and a respiratory rate of 18/min. Physical examination reveals difficulty performing rapid alternating movements and a tremor in his hands that appears while performing motor tasks, including writing. *These symptoms are most likely due to disease in which of the following structures?* A. cerebellum B. internal capsule C. primary motor cortex D. spinal cord E. substantia nigra

*cerebellum* This patient is most likely experiencing intention or kinetic tremor of his hands. Intention tremors are most characteristic of damage to the cerebellum or cerebellar pathways, especially the output from the dentate nucleus of the cerebellum to the ventral lateral nucleus of the thalamus. The most common causes of intention tremors are stroke, multiple sclerosis of the cerebellum, or midbrain trauma that affects cerebellar outflow. Degenerative diseases of the cerebellum, Wilson disease, hepatocerebral degeneration, and mercury poisoning may also lead to intention tremor. This tremor usually increases in severity as the hand moves closer to its target, which is in contrast to postural or action tremors that tend to remain constant throughout the range of the motion. Intention tremors are usually very large in amplitude due to the involvement of proximal muscles. Answer B: An internal capsule lesion would more commonly lead to upper motor neuron signs rather than cerebellar signs like intention tremor. Answer C: A lesion in the primary motor cortex is typically characterized by upper motor neuron signs rather than cerebellar signs like intention tremor. Answer D: A spinal cord lesion would more commonly lead to upper motor neuron signs or lower motor neuron signs rather than cerebellar signs like intention tremor. Answer E: A lesion in the substantia nigra is typically characterized by Parkinson disease, which causes resting tremor rather than intention tremor. Bottom Line: Intention tremor is seen in patients with cerebellar damage, which typically is caused by stroke, multiple sclerosis, or midbrain trauma.

A 56-year-old female with a past medical history of transitional cell bladder carcinoma presented for chemotherapy treatment and is started on appropriate medication. Two weeks later, she presents to your office with complaints of wrist drop and ringing in her ears. The most likely etiological agent is A. bleomycin B. busulfan C. cisplatin D. cyclophosphamide E. etoposide

*cisplatin* Cisplatin is an antineoplastic that alkylates and cross-links DNA. Cisplatin is used in the treatment of testicular, bladder, ovary, and lung carcinomas. Side effects include nephrotoxicity, acoustic nerve damage and resultant tinnitus, and peripheral neuropathy which can result in wrist or foot drops. Nephrotoxicity is prevented with the use of the free radical scavenger amifostine and chloride diuresis. Answer A: Bleomycin is an antineoplastic agent that inhibits DNA synthesis through free radical formation that induces single-strand breaks in DNA. Bleomycin inhibits DNA, RNA, and protein synthesis in the G2 and M phases of the cell cycle. It is used in the treatment of Hodgkin lymphoma and testicular cancer. Side effects of bleomycin include pulmonary fibrosis which results in a restrictive lung disease. Answer B: Busulfan is an antineoplastic that works by alkylating and cross-linking strands of DNA and is cell-cycle nonspecific. It is used for treatment in chronic myelogenous leukemia and to ablate a patient's bone marrow before bone marrow transplantation. Side effects include pulmonary fibrosis and hyperpigmentation. Answer D: Cyclophosphamide is an alkylating agent that prevents cell division by covalently cross-linking DNA strands at the guanine N-7 location and, thus, decreasing DNA synthesis. It requires initial activation by the liver. Side effects include myelosuppression and hemorrhagic cystitis. Hemorrhagic cystitis is due to the metabolite acrolein. It can be prevented with proper hydration and the use of the medication mesna. Answer E: Etoposide is a topoisomerase II inhibitor that leads to the inhibition of DNA synthesis. It primarily acts in the S and G2 phases of the cell-cycle. Etoposide is used in the treatment of small cell lung carcinoma and testicular carcinoma. Side effects include myelosuppression, gastrointestinal irritation, and alopecia. Bottom Line: Cisplatin is an antineoplastic that alkylates and cross-links DNA. Side effects include nephrotoxicity, ototoxicity, and peripheral neuropathy.

A 4-year-old male presents via his mother for generalized weakness. She describes her son as having increasing difficulties running, jumping and climbing up their stairs at home. His past medical history is significant for an upper airway infection a few months ago. The patient's family history is only significant for chronic anemia. On examination, temperature is 99ºF, heart rate is 83/minute, blood pressure is 98/64 mmHg, respiratory rate is 16/minute, and SpO2 is 99% on room air. He has a waddling, toe walking gait and lower extremity hyporeflexia. Osteopathic examination reveals a ropy texture with decreased bulk to both gluteus maximus muscles. Laboratory studies are shown below. Hemoglobin = 14.2 g/dL Hematocrit = 39.0% White blood cells = 6,400/mm3 Platelets = 320,000/mm3 *The most likely cause of these findings is due to:* A. complete disruption of the dystrophin gene B. absence of the fritaxin gene C. partial disruption of the dystrophin gene D. dysfunction of the fritaxin gene E. expansion of the CTG trinucleotide repeat

*complete disruption of the dystrophin gene* Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by a complete disruption in th function of the dystrophin gene. It presents between 3 to 5-years-old with proximal muscle weakness. The loss of dystrophin leads to myofibril membrane instability and degeneration of muscle fibers, which is replaced by fibrofatty tissue and causes pseudohypertrophy of the calf muscles. Patients present with a waddling, toe walking gait and a positive Gower's sign, in which the child uses his hands to walk up the legs from a seated position. Physical examination reveals pseudohypertrophy of the calf and (occasionally) quadriceps muscles, lumbar lordosis, shortening of the Achilles tendons, and hyporeflexia or areflexia. The molecular basis for the phenotypic differences among the dystrophinopathies is related in part to whether the reading frame for dystrophin is preserved. In most cases, patients with DMD have lesions that disrupt the reading frame for dystrophin, while those with Becker muscular dystrophy (BMD) have mutations that maintain the amino acid coding sequence. DMD may result from frameshift or early termination such that no functional dystrophin is produced. Osteopathic examination reveals chronic tissue texture changes in the gluteus maximus muscles, which demonstrate atrophy and a decreased ability to perform hip extension. This leads to posture compensation via an exaggerated lumbar lordosis, a waddling gait, and Gower's sign. Answers B & D: Friedreich ataxia is a hereditary disease that is caused by a mutation in the frataxin gene. Friedreich ataxia presents in childhood with neurologic dysfunction, cardiomyopathy, and diabetes mellitus. There is progressive ataxia of all four limbs due to cerebellar dysfunction and often manifests by 5-years-old. Proprioception, vibration, and deep tendon reflexes are lost. Patients typically develop hypertrophic cardiomyopathy which also serves as a frequent cause of death. The patient in this stem has no signs of cerebellar dysfunction (such as ataxia) but rather signs more indicative of proximal muscles weakness described as trouble running, jumping, and climbing stairs. In addition to the shortened Achilles tendons, most likely indicating calf hypertrophy, this patient's weakness is much more indicative of a muscular dystrophy. Answer C: Becker's muscular dystrophy is an X-linked disorder caused by a mutation producing a partially functional dystrophin protein. In contrast to Duchenne muscular dystrophy, Becker muscular dystrophy has a later age of onset (typically after age 10) and a milder clinical course due to a less severe muscle involvement. Patients can remain ambulatory well into adult life. This retained strength permits the clinical distinction between Becker's muscular dystrophy and Duchenne muscular dystrophy. Mental retardation is also not as common and often not as severe. This patient's age and degree of weakness is more consistent with Duchenne's muscular dystrophy. Answer E: Myotonic dystrophy is an autosomal dominant adult-onset muscular dystrophy that presents between 20 to 40-years-old. Myotonic dystrophy is characterized by skeletal muscle rigidity and slow relaxation of a muscle after contraction rather than hyporeflexia as seen in this patient. Additionally, muscle pain is extremely common in patients with myotonic dystrophy. Weakness occurs in muscles of the face and extremities. Patients often have a characteristic long and narrow face with a high arching palate. Patients tend to lose grip strength as muscle weakness progresses over time. *Bottom Line*: Duchenne and Becker muscular dystrophies are caused by mutations of the dystrophin gene. Duchenne muscular dystrophy results in a more severe clinical course due to a complete absence of the functional dystrophin protein. Becker muscular dystrophy has a later onset and a milder clinical course due to the production of a partially functional dystrophin protein.

A 65-year-old male presents to his primary care physician for a routine checkup. History reveals a 50-pack-year of cigarette smoking and chronic obstructive pulmonary disease. Physical examination reveals a distended abdomen with visible pulsations along the midline. Abdominal ultrasound reveals an abdominal aortic aneurysm of 6 cm. The patient is referred for surgery. During the repair, the surgeon ruptures an artery that supplements the anterior spinal artery near T8. *Which of the following neurological deficits is the most likely complication?* A. dec. motor strength and pain sensation in the lower extremities B. dec. motor strength and vibratory sensation in the lower extremities C. dec. pain and vibratory sensation in the lower extremities D. dec. pain and vibratory sensation in the upper extremities

*dec. motor strength and pain sensation in the lower extremities* The artery of Adamkiewicz arises from a left posterior intercostal artery and supplements the anterior spinal artery near the T8 spinal cord level. If the surgeon ruptures the artery of Adamkiewicz, this will cause deficits bilaterally below T8 related to the tracts supplied by the descending anterior spinal artery. The anterior spinal artery supplies the anterior 2/3 of the spinal cord, which includes the anterior horns, corticospinal tracts, and spinothalamic tracts. Anterior spinal cord lesions above C5 will result in tetraplegia with involvement of the upper and lower extremities, while lesions within the thoracic spinal cord will result in paraplegia with involvement of the lower extremities only. This patient will have clinical signs related to lesion of corticospinal tracts (weakness and hyperreflexia) and spinothalamic tracts (pain and temperature loss) for lower extremities but not upper extremities, because of rupture of the artery of Adamkiewicz. Tactile, position, and vibratory sensation are normal, because the posterior columns are unaffected, due to the posterior columns being supplied by the posterior spinal artery. Answer B: Although decreased motor strength is likely, vibration sensation will be spared, because the posterior columns responsible for tactile, position, and vibratory sensation are supplied by the posterior spinal arteries. Answer C: Although decreased pain sensation is likely, vibration sensation will be spared, because the posterior columns responsible for tactile, position, and vibratory sensation are supplied by the posterior spinal arteries. Answer D: The upper extremities would not have decreased somatosensation, because the artery of Adamkiewicz supplies the anterior spinal artery below T8, and the upper extremities are innervated by C5-T1 levels of spinal cord. *Bottom Line*: The anterior spinal artery supplies the anterior 2/3 of the spinal cord, including the corticospinal and spinothalamic tracts. The artery of Adamkiewicz feeds into the anterior spinal artery near T8. Rupture of the artery of Adamkiewicz will cause lower extremities to suffer loss of motor strength and loss of pain and temperature sensation.

A 25-year-old male presents to the emergency department with a puncturing knife wound just medial to the superior angle of the scapula. The muscle, which attaches to this location, was completely severed, along with the nearby artery. Bright red blood is continually leaking from the wound despite the pressure dressing applied by the paramedics. *Which of the following arteries divides around this scapular attachment and descends to the inferior angle of the scapula?* A. axillary a. B. circumflex a. C. dorsal scapular a. D. posterior circumflex humeral a. E. suprascapular a.

*dorsal scapular a.* This patient is suffering damage to the levator scapulae muscle and the dorsal scapular artery. This artery divides around the levator scapulae muscle at the superior angle of the scapular and descends along the medial aspect of the scapula, supplying the rhomboids and the medial half of the infraspinatus and teres major. This artery anastomoses with the infraspinatus branch of the suprascapular artery and the circumflex scapular artery to complete the anastomosis of the scapula. Therefore, blood supply to the medial border of the scapula is maintained by the circumflex scapular and suprascapular artery if damage of the dorsal scapular artery occurs. Answer A: The axillary artery is the continuation of the subclavian artery and begins at the border of the first rib. Descending through the axillae of the arm, it becomes the brachial artery at the lower border of the teres major. The axillary artery is divided into 3 sections: the superior thoracic, thoracoacromial, and subscapular divisions. Answer B: The circumflex scapular artery is present within the triangular space of the shoulder. Two arteries originate from the subscapular artery: the circumflex scapular artery, which runs posteriorly, and the thoracodorsal artery, which runs inferiorly along with the thoracodorsal nerve. The circumflex scapular artery is an important component of the scapular arterial anastomosis. Answer D: The posterior circumflex humeral artery is located within the quadrangular space. The space is bordered by the teres minor, the teres major, the long head of the triceps, and the medial humeral border. This artery branches from the third section of the axillary artery Answer E: The suprascapular artery is a branch from the thyrocervical trunk. This trunk comes directly from the subclavian artery and divides into the suprascapular artery, the transverse cervical artery, the ascending cervical artery, and the inferior thyroid artery. This artery supplies the supraspinatus and infraspinatus muscles. *Bottom Line*: The dorsal scapular artery divides around the levator scapulae muscle at the superior angle of the scapula and descends along the medial aspect of the scapula.

A 32-year-old male with a history of asthma and major depressive disorder presents to a primary care clinic complaining of difficulty ambulating. He complains of weakness, which started in his feet and has spread upward over the past 48 hours. History reveals that he returned from a weekend camping trip a week ago, during which he prepared his own food, including pancakes, eggs, pork sausage, orange juice, chicken, potatoes, carrots, and granola. He states that he had an episode of 3-day bloody diarrhea upon his return, but this has since resolved. Physical examination reveals normal respiratory effort and air entry without wheezes, crackles or rhonchi, and an abdomen that is nontender and nondistended with normoactive bowel tones in all 4 quadrants. Motor strength is 3/5 bilaterally in the feet, 4/5 bilaterally at the knees and hips, and 5/5 bilaterally in the upper extremities. *If the patient's stool from his earlier diarrheal episodes had been sent for laboratory analysis, laboratory evaluation would most likely have revealed the presence of* A. paramoxyvirus B. an orthomyxovirus C. cysts and trophozoites w/spherical nuclei D. gram-neg. curvy rods E. gram-neg. rods producing Shiga-like toxin

*gram-neg. curvy rods* This patient shows signs of Guillain-Barré syndrome (GBS), which is commonly precipitated by Campylobacter jejuni, Mycoplasma pneumoniae, cytomegalovirus, Epstein-Barr virus, or influenza infection. GBS involves autoimmune inflammation and demyelination of the peripheral nervous system and ventral (motor) roots, causing symmetrical ascending weakness. Most patients survive, but respiratory support is most important if the weakness spreads to the diaphragm. C. jejuni is a motile, oxidase-positive, gram-negative curved rod that grows at 42°C and is one of the most common causes of bloody diarrhea in the United States. Answer A: Paramyxoviruses belong to the Paramyxoviridae family, which includes the parainfluenza virus, respiratory syncytial virus (RSV), and measles virus. Parainfluenza virus and RSV primarily cause respiratory infections. Measles virus causes a rash that begins at the head and moves downward; the rash is preceded by a cough and blue-white lesions on the buccal mucosa ("Koplik spots"). There is no weakness associated with a paramyxovirus infection. However, there is a post-infection inflammatory disorder called acute disseminated encephalomyelitis that is very rare and can follow measles, mumps, rubella, influenza, and other viral infections. It is similar to multiple sclerosis and has a similar presentation because it has an autoimmune (non-infectious) etiology. This patient's presentation is more consistent with GBS. Answer B: Influenza A virus is a segmented RNA orthomyxovirus that has been associated with the development of GBS. However, this patient presents with bloody diarrhea, which is not associated with an influenza infection. Answer C: Entamoeba histolytica can cause bloody diarrhea because it invades the gastric mucosa. Secondary complications can include liver abscesses if the organism invades the liver. E. histolytica is acquired from contaminated food or water and is associated with camping. It is not associated with GBS. Answer E: Enterohemorrhagic Escherichia coli (EHEC) includes many strains of E. coli, such as O157:H7, which produces Shiga-like toxin. EHEC can cause bloody diarrhea, more commonly in children and the elderly. Secondary complications of EHEC include hemolytic uremic syndrome, but not GBS. *Bottom Line*: Campylobacter jejuni is one of the most common causes of bloody diarrhea in the United States and is associated with Guillain-Barré syndrome, which presents as ascending weakness.

A 50-year-old female presents to her family physician with complaint of dry eyes. History reveals that she keeps the shades drawn at home to prevent sunlight entry, she wears dark sunglasses outside, and she has tried moisturizing drops but only achieves temporary relief. Neurological examination reveals loss of tear production for the right eye, loss of the corneal reflex for the right eye, Bell palsy on the right side of the face, but no loss of somatosensation for either side of the face. *Which of the following additional clinical signs is most likely?* A. decreased salivary gland output on the R side B. hyperacusis on the R side C. inability to chew on the L side D. inability to chew on the R side E. loss of taste sensation on the R side of the tongue

*hyperacusis on the R side* A primary function of the facial nerve (cranial nerve VII) is innervation of the muscles of facial expression, with lesion of the facial nerve causing Bell palsy on the ipsilateral side. The corneal reflex is tested by touching cotton to one eye and observing blinking. The afferent limb of this reflex comprises somatosensory neurons of the ophthalmic division of the trigeminal nerve (cranial nerve V). The efferent limb comprises somatic motor fibers in the facial nerve that terminate in the orbicularis oculi muscles. Since somatosensation of the face is spared, a key function for the trigeminal nerve, the loss of the corneal reflex is due to a lesion of the facial nerve rather than the trigeminal nerve. The facial nerve also innervates the lacrimal gland, and when damaged causes a loss of tear production. Finally, the facial nerve innervates the stapedius muscle, so a lesion of the right facial nerve causes hyperacusis on the right side. Answer A: Decreased salivary gland output due to facial nerve lesion would be on the ipsilateral or right side for this patient, not the left side. Answer C: The mandibular division of the trigeminal nerve innervates the muscles of mastication. However, since the facial nerve is lesioned rather than the trigeminal nerve, there would be no effect on chewing ability on the left side or right side. Answer D: The mandibular division of the trigeminal nerve innervates the muscles of mastication. However, since the facial nerve is lesioned rather than the trigeminal nerve, there would be no effect on chewing ability on the right side or left side. Answer E: Loss of taste sensation due to facial nerve lesion would be on the ipsilateral or right side for this patient, not the left side. *Bottom Line*: The afferent limb of the corneal reflex is the trigeminal nerve and the efferent limb is the facial nerve, which also innervates the stapedius muscle. With no loss of face somatosensation, the trigeminal nerve is spared, and a loss of the corneal reflex is due to facial nerve lesion.

A 45-year-old patient with a history of human immunodeficiency virus (HIV) infection and CD4+ count of 45/mm3 presents with headache, stiff neck, and impaired mental status. A cerebrospinal fluid sample is obtained by lumbar puncture, and an India ink stain performed on the sample reveals heavily encapsulated yeast. One week after initiation of treatment, the patient has routine laboratory results drawn as shows hypokalemia and elevated BUN. *What is the mechanism of action for the medication that is most likely responsible for the abnormal laboratory results?* A. disturbs the integrity of the fungal cell wall via inhibition of fungal (1→3)-β-D-glucan-synthesis B. increases membrane permeability by binding to ergosterol in the fungal plasma membrane C. inhibits ergosterol synthesis D. interferes w/DNA synthesis making it a strong fungicidal agent E. interferes w/microtubule formation

*increases membrane permeability by binding to ergosterol in the fungal plasma membrane* Cryptococcus neoformans meningitis/encephalitis is an opportunistic infection that affects immunocompromised patients, specifically HIV/AIDS patients with CD4 counts below 50/mm3. It is an encapsulated yeast visible with India ink. C. neoformans is acquired via inhalation in contaminated bird droppings, specifically pigeons. Untreated cryptococcal meningitis is uniformly fatal, although survival can range from years in those without apparent immunocompromise to only a few weeks in HIV-associated infection. Optimal current therapy is with amphotericin B 0.7-1 mg/kg/day plus flucytosine 100 mg/kg/day for 2 weeks, followed by fluconazole 400 mg/day for 8 weeks and 200 mg/day thereafter. Amphotericin B, a polyene introduced in the 1950s, is a broad-spectrum fungicidal agent that binds to ergosterol in the fungal plasma membrane, increasing permeability to protons and monovalent cations such as potassium. Thus, it binds to ergosterol (amphotericin B for Bind) and forms pores in the fungal cell membrane. Major side effects of amphotericin include hypokalemia, hypomagnesemia, and renal impairments; therefore, it is important to check laboratory results frequently while on this medication. Saline loading reduces amphotericin B nephrotoxicity. Answer A: The cell wall of fungus is made of chitin. Caspofungin targets the fungal cell wall, but amphotericin does not. Caspofungin is the best drug for candidemia in neutropenic patients with fever. Voriconazole is the best drug for aspergillus; however, caspofungin may be used for invasive aspergillosis as well. Answer C: The azoles (like fluconazole) interfere with ergosterol synthesis. They bind to and inhibit fungal 14α-demethylase, an enzyme that converts lanosterol into ergosterol. The lack of ergosterol in the fungal cell membrane leads to loss of cellular stability and cell death. Fluconazole is used in prophylaxis of C. neoformans but is not a first-line agent in treatment. Though hypokalemia may occur with this medication, it is not as frequently seen; therefore, this is not the best answer choice. Answer D: Flucytosine (5-fluorocytosine [5FC]), was developed as an anticancer drug. Within cryptococcal cells, flucytosine is converted by cytosine deaminase (an enzyme present in fungi and bacteria but not in mammalian cells) to 5-fluorouracil (5-FU) a pyrimidine analogue that inhibits nucleic acid synthesis. Though hypokalemia may occur with this medication, it is not as frequently seen; therefore, this is not the best answer choice. Answer E: Griseofulvin is an antifungal drug that is administered orally. It is used both in animals and in humans, to treat fungal infections of the skin (commonly known as ringworm) and nails. Griseofulvin, used for dermatophytes, interferes with microtubule function. It is not used to treat C. neoformans. *Bottom Line*: Amphotericin B is the drug of choice for Cryptococcus neoformans infections in patients with AIDS. Hypokalemia, hypomagnesemia, and renal impairment are frequent adverse events.

A 30-year-old male presents to the emergency department with complaint of head trauma. History reveals that he was unrestrained in a motor vehicle accident 30 minutes earlier. As a result, he hit his head against the windshield and suffered a concussion that left him unconscious for 10 minutes. Physical examination reveals loss of somatosensation from his right upper and lower extremities, but normal somatosensation on the left side of his body. Neurological examination reveals a right homonymous hemianopia. Osteopathic cranial examination reveals a compression strain with a severely decreased cranial rhythmic impulse (CRI). Imaging reveals hemorrhage in the left thalamus. *Visual information is transmitted to the primary visual cortex of the visual pathway by way of which of the following thalamic nuclei?* A. lateral geniculate B. medial geniculate C. ventral lateral D. ventral posterolateral E. ventral posteromedial

*lateral geniculate* A compression strain of the sphenobasilar synchondrosis is a result of the sphenoid and occiput being pushed together. This could result from the head trauma this patient sustained in the motor vehicle accident. Compression strains will demonstrate a decreased CRI amplitude. Hemorrhage in the left thalamus can explain the symptoms and signs on the right side of the patient. For the right homonymous hemianopia, lesion of the visual pathway has to be in the left optic tract, lateral geniculate nucleus of the left thalamus, left optic radiations, or left primary visual cortex. Answer B: The medial geniculate nucleus receives auditory information from the inferior colliculus and the superior olivary complex and projects to the primary auditory cortex of the temporal lobe. Answer C: The ventral lateral nucleus receives input from the basal nuclei and cerebellum and projects to the primary motor cortex and the association motor cortices. It is involved in controlling and coordinating movement. Answer D: The ventral posterolateral nucleus receives somatosensory information from the body (medial lemniscus for light touch, vibration, and position sense; spinothalamic tract for pain and temperature sensation) and projects to the primary somatosensory cortex of the parietal lobe. Answer E: The ventral posteromedial nucleus receives somatosensory information from the face and projects to the primary somatosensory cortex of the parietal lobe. *Bottom Line*: The lateral geniculate nucleus of the thalamus receives visual information from the retina and projects to the primary visual cortex of the occipital lobe.

A 30-year-old female presents to her primary care physician with complaint of difficulty looking to her left. History reveals that this began 1 month earlier. Neurologic examination reveals normal vestibulo-ocular reflexes for both eyes. In addition, she can look straight ahead or track a pen light to the right. However, when she tries to track a pen light to the left, neither eye will rotate beyond the midline position. Ophthalmologic examination reveals normal direct and consensual pupillary responses with a pen light directed into either eye and no visual field defects. A lesion has occurred to which of the following structures? A. L abducens n. B. L frontal eye fields C. left paramedian pontine reticular formation D. right medial longitudinal fasciculus E. right oculomotor n.

*left paramedian pontine reticular formation* Voluntary horizontal eye movements are initiated by cortical eye fields. For saccades (shifting gaze from one stationary object to another), the frontal eye fields are primarily responsible. For smooth pursuit (tracking a moving object), cortical eye fields in multiple lobes of the brain are involved. For voluntary horizontal gaze to the left, right cortical eye fields activate the left paramedian pontine reticular formation (PPRF), which then activates the left abducens nucleus. Some neurons from the left abducens nucleus stimulate contraction of the left lateral rectus muscle through the abducens nerve. Other neurons from the left abducens nucleus activate a subset of neurons in the right oculomotor nucleus through the medial longitudinal fasciculus (MLF), with that subset of oculomotor neurons stimulating contraction of the right medial rectus muscle through the oculomotor nerve. Thus, the lateral rectus muscle of the left eye contracts in coordination with the medial rectus muscle of the right eye to cause voluntary horizontal gaze to the left. If the left abducens nerve has a lesion, the left eye will have paralysis of gaze to the left (abductor paralysis in left eye), but the right eye will be able to gaze to the left. If the right MLF has a lesion, the right eye will have paralysis of gaze to the left (adductor paralysis in right eye), but the left eye will be able to gaze to the left. For both eyes to have paralysis of voluntary horizontal gaze in one direction, either the contralateral cortical eye fields or ipsilateral PPRF is the site of the lesion. The clinical signs for this patient are consistent with lesion of the left PPRF. Answer A: If the left abducens nerve has a lesion, the left eye will have paralysis of gaze to the left (abductor paralysis in left eye), but the right eye will be able to gaze to the left. Thus, there would not be paralysis of voluntary horizontal gaze to the left for both eyes. Answer B: If the left frontal eye field has a lesion, there will be paralysis of voluntary horizontal gaze to the right, but gaze to the left will be spared. Thus, there would not be paralysis of voluntary horizontal gaze to the left for either eye. In addition, if the damage had been to the right frontal eye field, the paralysis would likely be transient because of bilateral cortical connections to brainstem gaze centers. Answer D: If the right MLF has a lesion, the right eye will have paralysis of gaze to the left (adductor paralysis in right eye), but the left eye will be able to gaze to the left. Thus, there would not be paralysis of voluntary horizontal gaze to the left for both eyes. Answer E: If the right oculomotor nerve has a lesion, the right eye will have paralysis of gaze to the left (adductor paralysis in right eye), but the left eye will be able to gaze to the left. In addition there would be ptosis (drooping eyelid) and mydriasis (dilated pupil). Thus, there would not be paralysis of voluntary horizontal gaze to the left for both eyes. Bottom Line: For both eyes to have paralysis of voluntary horizontal gaze in one direction, either the contralateral cortical eye fields or ipsilateral paramedian pontine reticular formation is the site of the lesion.

A 45-year-old female presents to her psychiatrist with continuing complaint of depression. History reveals that during the past 6 months, she has experienced fatigue, loss of concentration, loss of interest in formerly interesting activities, depressed mood, and insomnia. She was diagnosed as having a major depressive disorder 3 months ago, but selective serotonin reuptake inhibitors (SSRIs) have been ineffective. As an alternative, her psychiatrist prescribes nortriptyline to treat her depression. This medication preferentially targets which of the following structures of the brain linked to depression but not targeted by SSRIs? A. caudate nucleus B. locus ceruleus C. pontine nucleus D. raphe nucleus E. substantia nigra

*locus ceruleus* The most widely prescribed antidepressants are selective serotonin reuptake inhibitors (SSRIs), including Prozac, Zoloft, and Paxil. Tricyclic antidepressants (TCAs) are an older class of antidepressants with more severe adverse events. They are usually prescribed only if newer antidepressants like SSRIs are ineffective. Nortriptyline is a TCA that preferentially inhibits norepinephrine reuptake and, to a lesser extent, serotonin. The locus coeruleus of the pons has been linked to clinical depression and is the primary site of norepinephrine synthesis in the brain. Increased norepinephrine release from the locus coeruleus correlates with anxiety and mania, whereas decreased norepinephrine release correlates with depression. Studies have demonstrated that nortriptyline can improve the clinical outcome for patients with depression and may be prescribed for patients for whom SSRIs are ineffective because nortriptyline targets the locus coeruleus whereas SSRIs do not. The figure illustrates a cross section at the level of the rostral pons showing the location of locus coeruleus. Answer A: The caudate nucleus is part of basal nuclei circuitry and is involved in the control of learned stereotyped movements but is not linked to depression. It contains GABAergic (inhibitory) and cholinergic (excitatory) neurons, so nortriptyline would have little effect. Answer C: Pontine nuclei are part of cerebellum circuitry and are involved in the coordination of movement but are not linked to depression. They contain glutamatergic neurons (excitatory), so nortriptyline would have little effect. Answer D: The raphe nuclei are located in the brainstem, contain neurons that project throughout the brain, and are linked to depression. They contain serotonergic neurons (inhibitory). This area is targeted by SSRIs, but SSRIs have been ineffective for this patient. Any inhibition of serotonin reuptake by nortriptyline would also be ineffective. Nortriptyline preferentially inhibits norepinephrine reuptake, and if it alleviates depression for this patient, it will do so by inhibiting norepinephrine reuptake at the locus coeruleus. Answer E: The substantia nigra is located in the midbrain, is part of basal nuclei circuitry, and is involved in the control of learned stereotyped movements, but it is not linked to depression. It contains dopaminergic neurons (excitatory and inhibitory), so nortriptyline would have little effect. *Bottom Line*: The locus coeruleus of the pons has been linked to clinical depression and is the primary site of norepinephrine synthesis in the brain. Nortriptyline is a tricyclic antidepressant that preferentially inhibits reuptake of norepinephrine and, to a lesser extent, serotonin. Nortriptyline can improve the clinical outcome for patients with depression.

A 75-year-old male presents with a progressive loss of memory. He has had past episodes of disorientation in which he has gotten lost driving home from the grocery store. He was recently found by the police wandering the streets in the middle of the night. Treatment will most likely include A. amantadine B. haloperidol C. levodopa D. memantine E. selegiline

*memantine* This patient is presenting with Alzheimer's dementia. Acetylcholine is the neurotransmitter most affected in this disease, and the use of acetylcholinesterase inhibitors are used to increase the levels of acetylcholine in the central nervous system. These agents act to reversibly inhibit acetylcholinesterase, which is the enzyme that catabolizes acetylcholine. These agents include donepezil, galantamine, rivastigmine, and tacrine. Memantine is a NMDA receptor antagonist that is also used for Alzheimer dementia, often in combination with acetylcholinesterase inhibitors. Answer A: Amantadine is used for the treatment of Parkinsonism caused by the use of antipsychotic medications. It is also used in the prophylaxis and treatment of influenza A. Its mechanism of action is thought to be due to blocking the reuptake of dopamine into presynaptic neurons or by increasing dopamine release from presynaptic fibers. Side effects of amantadine include orthostatic hypotension, depression, and cardiac arrhythmias. Answer B: Haloperidol is an antipsychotic medication that acts by antagonizing dopamine D2 receptors. It is used to treat the aggressive behavior, hostility, and violence that sometimes occurs in patients with dementia. Side effects include extrapyramidal effects such as acute dystonia, Parkinsonism, and tardive dyskinesia. Answer C: Levodopa is a precursor of dopamine that crosses the blood-brain barrier to increase levels of dopamine in the nigrostriatal pathway. It is used in the treatment of Parkinson disease and Parkinsonism syndrome caused by antipsychotic medication usage. Side effects include nausea, vomiting, hypotension, and the "on-off" phenomenon in which levodopa becomes less effective over time. In the off state, the patient becomes very stiff and unable to move. Answer E: Selegiline acts by inhibiting monoamine oxidase B, which is involved in the deamination of dopamine in the central nervous system. Thus, selegiline results in increased levels of dopamine in the CNS. Selegiline is used in the treatment of atypical depression and Parkinson disease. *Bottom Line*: Memantine is an NMDA receptor antagonist that is used as adjuvant therapy in those with Alzheimer dementia.

A 55-year-old male presents to the emergency department with nausea and vomiting. History reveals an acute onset that began 2 hours ago. Physical examination reveals uvula deviation to the right, diminished gag reflex, hoarseness of voice, and ptosis and miosis. When testing for pin prick sensation, the left side of the face and right side of the body have decreased response. The most likely involved structures are derived from which of the following secondary brain vesicles? A. diencephalon B. mesencephalon C. metelencephalon D. myelencephalon E. telencephalon

*myelencephalon* This patient is presenting with symptoms of an acute stroke of the lateral medulla. This condition is called lateral medullary syndrome or Wallenberg syndrome. This occurs with occlusion or rupture of the vertebral artery or, less commonly, the posterior inferior cerebellar artery. Structures of the lateral medulla that can be lesioned include the spinal trigeminal nucleus and tract, spinothalamic tract, vestibular nuclei, hypothalamospinal tract, restiform body, and nucleus ambiguus, leading to the clinical signs in this patient. During embryonic development, the cranial end of the neural tube divides into 3 primary brain vesicles that then divide into 5 secondary brain vesicles. These differentiate into specific brain regions. The medulla, as the most caudal part of the brain, forms from the myelencephalon, the most caudal of these secondary brain vesicles. Answer A: The diencephalon differentiates into the thalamus, hypothalamus, and other structures. Answer B: The mesencephalon differentiates into the midbrain. Answer C: The metencephalon differentiates into the cerebellum and pons. Answer E: The telencephalon differentiates into the cerebral hemispheres and deep brain structures. *Bottom Line*: During development, the cranial end of the neural tube divides into 3 primary brain vesicles that then divide into 5 secondary brain vesicles. These differentiate into the cerebral hemispheres and brainstem.

A 55-year-old male presents with intractable headaches that are worst upon waking up in the morning. Magnetic resonance imaging reveals a mass lesion located in his frontal lobe. A biopsy is performed which reveals compact rounded cells with a clear cytoplasm that surrounds a dense nucleus. There is also an abundant amount of finely branching capillaries present. *The most likely description of this patient's mass lesion is* A. craniopharyngioma B. glioblastoma multiforme C. meningioma D. oligodendroglioma E. pilocytic astrocytoma

*oligodendroglioma* Oligodendrogliomas are primary CNS tumors that most commonly occur in patients in the fourth to sixth decades of life. Oligodendrocytes are normally cells that myelinate axons in the central nervous system. Patients with oligodendrogliomas will present with headaches, seizures, confusion, cognitive dysfunction, focal weakness, sensory abnormalities, or aphasia. Most oligodendroglial tumors arise in the white matter of the cerebral hemispheres, predominantly in the frontal lobes. Histopathological examination of oligodendrogliomas will reveal a "fried-egg" appearance, which is due to multiple compact, rounded cells with clear cytoplasm that surround a dense central nucleus. Another characteristic pattern seen is the appearance of a vast vasculature of finely branching capillaries that give it the appearance of chicken wire. Answer A: Craniopharyngiomas are benign tumors of the CNS located in the sella turcica and most commonly occur in children aged 5 to 10-years-old. Craniopharyngiomas arise from Rathke's pouch, which is an embryologic structure that forms the infundibulum and anterior pituitary gland. Patients will present with symptoms of increased intracranial pressure, such as headaches, projectile vomiting, papilledema, a decrease in visual acuity, blurred vision, or bitemporal hemianopsia. Bitemporal hemianopsia results from an anterior extension of the tumor that puts pressure onto the optic chiasm. Craniopharyngiomas have both a solid and cystic component, and microscopic examination will reveal abundant cholesterol crystals in the fluid. Calcification of the tumor also occurs. Spillage of the cyst fluid into the subarachnoid space can result in chemical arachnoiditis. Answer B: Glioblastoma multiforme is a malignant tumor of the CNS that most commonly occurs in the cerebral hemispheres of adults over the age of 50-years-old. Patients will present with headaches, insidious onset of motor weakness, nausea, vomiting, cognitive impairment, or new onset seizures. Glioblastoma multiforme is composed of poorly differentiated, astrocytic cells with nuclear atypia and central necrosis from myelin breakdown. Most glioblastomas of the cerebral hemispheres are intraparenchymal in location and located in the cerebral white matter. Answer C: Meningiomas are CNS tumors that arise contiguously to the meninges. They arise from cells in the arachnoid layer that cover the surface of the brain. Meningiomas commonly are found at the surface of the brain, either over the convexity or at the skull base. The incidence of meningiomas increases with age, with an increased occurrence in patients older than 35-years-old. Patients will present with new onset seizures, focal weakness, dysphasia, apathy, somnolence, and new onset seizures due to irritation and compression of the underlying cortex. Meningiomas are well-demarcated neoplasms that have an attachment to the dura. A histopathological examination will reveal densely packed interlacing spindle cells that are arranged in sheets and contain calcified whorls, which are known as psammoma bodies. Answer E: Pilocytic astrocytomas are benign CNS neoplasms that most commonly present in the first two decades of life. They arise from astrocytes and are most commonly located in the cerebellum. Patients will present with symptoms of increased intracranial pressure due to a resultant hydrocephalus or mass effect. These symptoms include a headache, nausea, vomiting, irritability, ataxia, and visual complaints. Focal neurological deficits such as weakness, paralysis, sensory deficits, cranial nerve palsies, and seizures may also occur. CT or MRI will reveal a unilocular or multilocular cyst with an associated tumor nodule. A histological evaluation will reveal the presence of Rosenthal fibers, which are elongated corkscrew shaped eosinophilic fibers that stain positively for glial fibrillary acidic protein (GFAP).

A 27-year-old male presents to the clinic for weakness in his left leg. He reports that he recently returned home from Africa after studying abroad. He reports recently enduring 2 days of nausea, vomiting, sore throat, headache, and diarrhea that ended 3 days ago. History reveals that the patient has never been vaccinated due to personal beliefs. Physical examination reveals a positive Kernig sign along with muscle weakness, decreased reflexes, and fasciculations in the left leg. A lumbar puncture is performed and cerebrospinal fluid samples display elevated protein with prominent lymphocytic infiltrates, and polymerase chain reaction is positive for a single-stranded, linear RNA virus with an icosahedral capsid. *The most likely etiologic agent is a(n)* A. bunyavirus B. orthomyxovirus C. picornavirus D. polyomavirus E. reovirus

*picornavirus* Picornaviridae is a family of non-enveloped, single-stranded, positive sense, linear RNA viruses with icosahedral capsids. This virus family includes poliovirus, the viral agent responsible for causing the poliomyelitis seen in this patient. Although 99% of polio is eradicated from the Americas, Europe, and the Western Pacific, it still is encountered in the developing world. Other members of the Picornaviridae family include echovirus, enterovirus, rhinovirus, coxsackievirus, and hepatitis A virus. Poliovirus is transmitted by the fecal-oral route and initially replicates in the oropharynx before spreading distally into the gastrointestinal tract, followed by viremia and potential spread into the central nervous system (CNS). Once the virus gains access to the CNS, it can lead to the lytic destruction of cells in the anterior horn of the spinal cord, leading to lower motor neuron destruction. Clinically, this will manifest as profound asymmetric muscle weakness, fasciculations, and decreased reflexes secondary to lower motor neuron damage. Answer A: Bunyaviridae is a family of enveloped, single-stranded, negative sense, circular RNA viruses with 2 genome segments and helical capsids. This virus family includes the California encephalitis serogroup (eg, La Crosse virus) that is transmitted by mosquito bites and hantavirus that is spread by aerosolized rodent excretions and causes a severe pulmonary syndrome. These viruses are not associated with flaccid paralysis. Answer B: Orthomyxoviridae is a family of enveloped, single-stranded, negative sense, linear RNA viruses with 8 genome segments and helical capsids. This virus family includes the influenza virus, which typically presents with a severe respiratory infection, high fever, headache, dry cough, and myalgias. Answer D: Polyomaviridae is a family of non-enveloped, double-stranded, circular DNA viruses with icosahedral capsids. This virus family is endemic in human populations, causes lifelong infections, and includes the JC virus that leads to progressive multifocal leukoencephalopathy in the immunocompromised patient. Another member is the BK virus that is associated with reactivation and nephropathy in the kidney transplantation recipient. This patient is not immunosuppressed and does not show signs of progressive demyelination. Answer E: Reoviridae is a family of non-enveloped, double-stranded, linear RNA viruses with 10-12 segments and icosahedral capsids. Notable members of this virus family includes the tick-borne Colorado tick fever virus and fecal-oral spread rotavirus, which is a major cause of fatal diarrhea in children. Reoviruses are not typically indicated in CNS invasion and pathogenesis. *Bottom Line*: Poliovirus, a member of the Picornaviridae family, is a non-enveloped, single-stranded, positive sense, linear RNA virus that can induce motor neuron destruction and flaccid paralysis in a small percentage of infections. It is prevented by the inactivated (Salk) or live-attenuated (Sabin) vaccine.

A 76-year-old male presents to the emergency department with complaint of fatigue and general weakness. History reveals hypertension. Physical examination reveals hemiparesis in his upper and lower extremities on the left side, as well as hemianesthesia for the left side of the body and face. Visual field examination is unremarkable. *Which of the following is the most likely location for a stroke causing these clinical signs?* A. genu of the internal capsule B. lateral geniculate nucleus of the thalamus C. posterior limb of the internal capsule D. ventral posteromedial nucleus of the thalamus E. ventral posterolateral nucleus of the thalamus

*posterior limb of the internal capsule* The lenticulostriate arteries that supply the internal capsule are the most common site of spontaneous hypertensive hemorrhage in patients with long-standing hypertension. Other risk factors for hypertensive hemorrhage include aging, diabetes mellitus, hyperlipidemia, and smoking. Depending on the severity of the hemorrhage, part or all of the internal capsule may be affected. The *posterior limb of the internal capsule* contains the descending corticospinal tract (upper motor neurons for the extremities), as well as all ascending somatosensory pathways for the body and face. At the level of the internal capsule, all of these pathways are for the contralateral side of the body and face, and lesion will lead to contralateral hemiparesis and hemianesthesia. The genu of the internal capsule contains the descending corticonuclear (corticobulbar) tract (upper motor neurons for the face). Various nuclei in the thalamus are relay points for different pathways: lateral geniculate nucleus for visual system, ventral posterolateral nucleus for somatosensory pathways from the body, and ventral posteromedial nucleus for somatosensory pathways from the face. Answer A: Lesion of the internal capsule genu would result in motor losses from the contralateral side of the face, but not the body. None of the observed somatosensory signs would be present. Answer B: Lesion of the lateral geniculate nucleus of the thalamus would result in the visual field deficit of contralateral homonymous hemianopia due to disruption of the visual pathway. None of the observed motor or somatosensory signs would be present. Answer D: Lesion of the ventral posterolateral nucleus of the thalamus would result in loss of somatosensation from the contralateral side of the body, but not the face. None of the observed motor signs would be present. Answer E: Lesion of the ventral posteromedial nucleus of the thalamus would result in loss of somatosensation from the contralateral side of the face, but not the body. None of the observed motor signs would be present. Bottom Line: The posterior limb of the internal capsule contains the descending corticospinal tract and all ascending somatosensory pathways. Lesion leads to contralateral hemiparesis and hemianesthesia.

A 61-year-old man presents to your family practice clinic with complaints of a dry mouth and weakness. He states he has been having trouble standing up from a seated position. His social history is significant for a 55 pack-per-year smoking history. He also reports episodes of severe dyspnea coupled with intermittent hemoptysis. Plain film radiographs of his chest reveal a nodule located in the central part of his right middle lobe. *The most likely cause of his weakness is due to antibodies against* A. post-synaptic ACh receptors B. presynaptic Ca+ channels C. thyroid peroxidase D. TSH receptor E. tissue transglutaminase

*presynaptic Ca+ channels* The patient has clinical evidence of lung cancer based on his age, respiratory symptoms, and chest radiograph. He also has associated weakness of his lower extremities combined with some autonomic dysfunction of his mouth. These are clues to a paraneoplastic syndrome from a lung carcinoma that is causing him weakness. Lambert-Eaton syndrome is a presynaptic disorder of neuromuscular transmission in which there is reduced acetylcholine release from the presynaptic nerve terminals. This is due to antibodies developed against voltage-gated calcium channels, which interferes with the normal calcium flux required for the release of acetylcholine. This leads to proximal muscle weakness, depressed tendon reflexes, and autonomic changes. Weakness is the major symptom. Weak muscles may ache and are occasionally tender. Lower extremity muscles are affected predominantly, and patients will present with limb weakness. Patients typically have difficulty rising from a chair, climbing stairs, and walking. Dry mouth is the most common autonomic symptom while erectile dysfunction is common in men. Approximately one-half of patients with Lambert-Eaton syndrome are associated with a malignancy, most commonly a paraneoplastic syndrome caused by small cell lung cancer. In about 50% of patients, strength may improve after exercise. The diagnosis is clinical but confirmed by the presence of anti-voltage-gated calcium channel antibodies, and by electrodiagnostic studies. Repetitive nerve stimulation studies confirm the diagnosis by demonstrating facilitation. Answer A: Myasthenia gravis is an autoimmune disease leading to fluctuating muscle weakness and fatigue. Weakness is caused by circulating antibodies that block acetylcholine receptors at the postsynaptic neuromuscular junction, inhibiting the excitatory effects of the neurotransmitter acetylcholine on nicotinic receptors throughout neuromuscular junctions. The basic pathology is a reduction in the number of acetylcholine receptors at the postsynaptic muscle membrane. The usual initial complaint is extraocular muscle weakness or ptosis. The severity of the weakness typically fluctuates over hours, being least severe in the morning and worse as the day progresses. The weakness is increased by exertion and alleviated by rest. Weakness tends to spread from the ocular to facial to bulbar muscles and then to the trunk. Myasthenia gravis is treated medically with acetylcholinesterase inhibitors like physostigmine, pyridostigmine, and rivastigmine. Answer C: Hashimoto's thyroiditis is the most common cause of hypothyroidism. Symptoms of Hashimoto's thyroiditis include myxedema, weight gain, depression, sensitivity to cold, paresthesias, fatigue, bradycardia, high cholesterol, constipation, muscle weakness, infertility, and hair loss. The thyroid gland may become firm and large. Enlargement of the thyroid is due to lymphocytic infiltration and fibrosis. Hashimoto's thyroiditis is due to antibodies against thyroid peroxidase and thyroglobulin that cause a destruction of the follicles in the thyroid gland. The mainstay of treatment is with levothyroxine. Answer D: Graves' disease is a cause of hyperthyroidism. Signs include exophthalmos, goiter, and pretibial myxedema. Symptoms include insomnia, hand tremor, excessive sweating, heat intolerance, weight loss despite an increased appetite, diarrhea, palpitations, and muscle weakness. Diagnosis is confirmed by elevated serum levels of free T3 and T4, along with a low thyroid-stimulating hormone. Thyroid stimulating antibodies are detectable in the serum. Treatment is with propylthiouracil, methimazole, or radioactive iodine. Answer E: Celiac disease is a gluten-sensitive enteropathy caused by proteins in wheat, barley, and rye. Anti-endomysial, anti-gliadin, and anti-tissue-transglutaminase antibodies are diagnostic. The classic description of celiac disease includes the symptoms of malabsorption such as steatorrhea, weight loss, or a fat-soluble vitamin deficiency. There is a characteristic presence of histologic changes of villous atrophy on small intestinal biopsy. The appropriate treatment is a gluten-free diet for life. Bottom Line: Lambert-Eaton myasthenic syndrome is a disorder of the neuromuscular junction transmission of acetylcholine. It most commonly occurs as a neoplastic syndrome in a patient with small cell lung carcinoma.

A 25-year-old female, with a history of major depression, presents to the emergency department with her mother. The patient was found with an empty bottle of her medication in her room. She is agitated and confused. She has had 3 episodes of emesis and now is having diarrhea. Vital signs reveal a temperature of 39.3°C (102.7°F), a blood pressure of 194/98 mmHg, a heart rate of 108/min, a respiratory rate of 22/min, and an oxygen saturation of 96% on room air. Physical examination reveals an anxious and restless female, oriented only to self. She is diaphoretic, and mydriasis is noted. Deep tendon reflexes of the upper extremity are 3+ and the lower extremities are 4+ with myoclonus. A tremor is noted, without signs of rigidity. An ECG is unremarkable except for sinus tachycardia. Labs indicate an increased creatine phosphokinase. *The most likely diagnosis is* A. hypertensive crisis B. malignant hyperthermia C. neuroleptic malignant syndrome D. serotonin syndrome E. TCA overdose

*serotonin syndrome* This patient is presenting with a history of major depression, with an empty bottle found of her medication, which is most likely the medication used to treat her depression. The patient's clinical presentation is consistent with serotonin syndrome, which includes cognitive impairments, autonomic instability, and somatic effects. Hyperreflexia is the distinguishing feature that is seen in serotonin syndrome that would not be expected in other overdose situations. Serotonin syndrome is a direct result of elevated serotonin in the body. It usually occurs when there is an overdose of medications or when drugs that potentiate the effects of serotonin or elevate serotonin levels in the body are combined. Such drugs include serotonin reuptake inhibitors, tricyclic amine antidepressants, monoamine oxidase inhibitors, and decongestants with pseudoephedrine activity. Clinical presentation is widespread and includes the following triad of clinical symptoms: Cognitive impairment: Symptoms include anxiety, agitation, delirium, restlessness, and disorientation. Patients may startle easily. Autonomic instability: This includes diaphoresis, tachycardia, hyperthermia, hypertension, vomiting, mydriasis, and diarrhea. Neuromuscular hyperactivity: This can manifest as tremor, myoclonus, and hyperreflexia. Hyperreflexia and clonus are characteristic. Management of serotonin syndrome includes discontinuing the serotonergic agents, normalization of vital signs through supportive care, sedation with benzodiazepines, and administration of the serotonin antagonist cyproheptadine. Answer A: Hypertensive crisis presents with severe hypertension that causes end organ symptoms, as well as tachycardia, cardiac arrhythmias, and stroke. It occurs in the setting of monoamine oxidase inhibitors if too much is ingested, if it is combined with other drugs that potentiate catecholamine activity, or when a strict diet avoiding tyramine (eg, wines, cheeses) is not adhered to. Although monoamine oxidase inhibitor toxicity would cause hypertension and agitation, it would not cause hyperreflexia, which is a characteristic of serotonin syndrome. This answer is incorrect. Answer B: Malignant hyperthermia is a life-threatening condition that occurs in those with an inherited genetic mutation of the ryanodine calcium channel receptor responsible for calcium release within the sarcoplasmic reticulum of skeletal muscle. When exposed to anesthetic agents during surgery, this receptor is activated, leading to prolonged muscle contraction that causes tachycardia, tachypnea, hyperthermia, acidosis, and muscle rigidity and can potentiate rhabdomyolysis. This patient had hyperreflexia, not rigidity. In addition, there is no history of recent surgery that would cause this. This is incorrect. Answer C: Neuroleptic malignant syndrome (NMS) occurs as an adverse drug reaction to antipsychotic medication. It is caused due to increased dopamine blockade throughout the body. NMS is characterized by autonomic instability, muscle rigidity, and a high fever. Clinical presentation is similar to malignant hyperthermia, so a careful history is needed. In contrast to serotonin syndrome, NMS has decreased reflexes and muscle rigidity. Hyperreflexia and clonus would not be seen in NMS. This is not the best answer choice. Memory aid: The mnemonic FEVER has been devised to aid in remembering the clinical manifestations of fever, encephalopathy, vital signs that are unstable, elevated creatine phosphokinase due to muscle breakdown, and rigidity of muscle. Answer E: Although tricyclic antidepressants inhibit reuptake of both serotonin and norepinephrine, the predominant clinical features are that of both histamine and cholinergic receptor antagonists, which leads to dry mouth, constipation, and urinary retention. Toxicity causes a potentially fatal arrhythmia related to QT interval prolongation. Although the anti-cholinergic effect leads to tachycardia and elevated temperature, hyperreflexia and diarrhea would not be expected. In addition, the ECG was normal without signs of QRS widening, which would be characteristic of a tricyclic antidepressant overdose. This is incorrect. *Bottom Line*: Serotonin syndrome is characterized by a triad of cognitive impairment, autonomic instability, and somatic effects. Clinical presentation is widespread and includes tachycardia, hypertension, hyperthermia with diaphoresis and shivering, facial flushing, mydriasis, and muscle rigidity with myoclonus leading to rhabdomyolysis. Management of serotonin syndrome includes discontinuing the serotonergic agents, normalization of vital signs through supportive care, sedation with benzodiazepines, and administration of the serotonin antagonist cyproheptadine.

A 67-year-old Caucasian male with a past medical history of non-insulin dependent diabetes mellitus presents to his primary care physician with a progressive tightening of his hand muscles. He is very worried that he will not be able to play the Banjo anymore. He states that his father had a similar problem in his right hand when he was alive and was not able to garden. Observation reveals his left fist to be clenched. Palpation of his palm reveals thickened and tight skin with one nontender nodule. Sensation to temperature, vibration and touch are intact bilaterally to the dorsal and ventral aspects of the upper extremity. When asked to unclench his fist and extend his fingers, the digit(s) you would predict to be permanently contracted is/are A. all phalanges will be maintined in a claw like pattern B. the 1st digit C. the 4th and 5th digit D. the 2nd digit E. the 3rd digit and thumb

*the 4th and 5th digit* The fourth and the fifth digits are unable to extend in the classic *Dupuytren's contracture*. Dupuytren's contracture is a painless thickening and contracture of palmar fascia beneath the skin. One or both hands may be affected. The fourth digit is affected most often, followed by the fifth, then the third. The index fingers may be involved. Typically, a small, painless nodule develops in the connective tissue below the skin on the palmar aspect of the hand. Over time, it thickens into a cord-like band and leads to an inability to extend or straighten the fingers. Dupuytren's contracture can be associated with diabetes mellitus and may also be genetic. It is usually seen in caucasian males over 50 years of age. Treatment varies depending on severity and is geared towards improving the motion and flexibility of the fingers. If the palm is painful, glucocorticoid injection can be used for analgesia. Moderate to severe cases require fasciectomy. Answer A: Contraction of every finger in a claw-like fashion is caused by lesions of the median and ulnar nerve. This neuropathy would cause inherent weakness of the hand muscles and possible sensory deficits, neither of which the patient in the above scenario has. Claw-like deformity also does not involve palmar fascia thickening or nodules. Answer B: Gamekeeper's thumb is an injury to the ulnar collateral ligament leading to weakness and carpal instability. Patients complain of pain in the thumb, especially with extension and abduction. It does not cause contractures of the digit(s) nor thickening of the palmar fascia nor nodules. Answer D: Trigger finger, also called stenosing flexor tenosynovitis, is a solo contracture, often affecting the second digit. Patients usually complain of a catching sensation of the digit with use. It is a process of mechanical impingement and tendon entrapment. Trigger finger does not involve palmar fascia thickening, which is the case in the above scenario. The patient in the above scenario does not complain of a locking sensation in his digit(s), making the diagnosis of trigger finger less likely. Answer E: This is not a classic site for contractures and would indicate possible tendonitis or traumatic scarring. Bottom Line: Classic Dupuytren's contracture involves the fourth and fifth digits and is commonly associated with diabetes mellitus.

A 16-year-old male presents for evaluation of right hand weakness. He reports a skateboarding accident over 2 months ago in which he landed on the medial aspect of his right wrist. He reports intermittent numbness in his fourth and fifth digits and difficulty grasping objects. He denies any pain. He has no prior medical history and does not take any medications. He has an allergy to penicillin. Vital signs are temperature 36.9ºC (98.5ºF), heart rate 78/min, blood pressure 110/55 mmHg. Examination of his hand at rest is shown in the exhibit attached. *Muscle strength examination would most likely reveal loss of* A. arm abduction beyond 90 degrees B. forearm supination C. lateral finger flexion D. thumb adduction E. wrist extension

*thumb adduction* This patient is suffering from ulnar nerve damage at the wrist. Ulnar nerve damage is demonstrated by a claw hand that results from injury to the ulnar nerve. Digits four and five are mainly affected. The claw hand deformity is flexion of the proximal interphalangeal joints and distal interphalangeal joints along with metacarpophalangeal joint hyperextension of the fourth and fifth digits as shown in the image provided. The ulnar nerve is comprised of nerve roots C8-T1 and is responsible for abduction and adduction of the fingers. It also innervates the adductor pollicis muscle, which is responsible for thumb adduction. The adductor pollicis is the only muscle of the thenar eminence innervated by the ulnar nerve; the rest are innervated by the median nerve. The claw hand deformity of ulnar neuropathy appears similar to the "hand of benediction" deformity of median neuropathy, since digits four and five are flexed. The difference is in ulnar neuropathy, the hand is at rest with digits four and five flexed; whereas, in median neuropathy, the patient is actively trying to make a fist, but cannot close digits one, two, and three. The patient in the above scenario displays the hand in the image provided at rest, and therefore, demonstrates ulnar neuropathy. Proximal injuries to the ulnar nerve result in less obvious clawing due to damage to the ulnar half of flexor digitorum profundus. Answer A: Loss of arm abduction beyond 90 degrees is seen in shoulder dislocations, axillary nerve injury, or supraspinatus tears. Answer B: Forearm supination is mainly a function of the musculocutaneous nerve innervating the biceps brachii. Since the patient is complaining of numbness and weakness of digits 4 and 5, he is suffering from neuropathy of the ulnar nerve, which does not control forearm supination. Therefore, actions of the musculocutaneous nerve would remain intact. Answer C: The anatomical position of the hand is palms anterior, with medial referring to digits 4 and 5 and lateral referring to digits 1 and 2. Loss of lateral finger flexion is seen in median nerve damage from a supracondylar humerus fracture or from carpal tunnel syndrome. This causes a "hand of benediction" deformity, which looks similar to the ulnar neuropathy claw hand; however, it is seen when the patient actively tries to make a fist, whereas the ulnar claw is seen at rest. Since this patient is suffering this claw deformity at rest, he exhibits ulnar rather than median neuropathy. Answer E: Loss of wrist extension (wrist drop) is seen in radial nerve damage from a midshaft humerus fracture. The radial nerve courses through the radial groove with the deep artery of the arm. Since the patient is complaining of numbness and weakness of digits 4 and 5, he is suffering from neuropathy of the ulnar nerve, which does not control wrist extension. Therefore, actions of the radial nerve would remain intact. *Bottom Line*: Thumb adduction is a function of the ulnar nerve and is the only thumb movement not controlled by the median nerve. Weakness of the intrinsic muscles of digits 4 and 5 as well as thumb adduction is caused by ulnar neuropathy usually as a result of trauma.

A 55-year-old male presents to the emergency department with complaint of nausea, vomiting, headache, and left-sided weakness. History reveals that he was involved in a motor vehicle accident 30 minutes earlier. Physical examination reveals his right pupil to be fixed and dilated with the eye directed inferiorly and laterally and with ptosis of the right eyelid. He also has hemiparesis of the left upper and lower extremities but no somatosensory loss. *Which of the following is the most likely cause of this patient's symptoms?* A. anterior communicating artery rupture B. posterior inferior cerebellar a. occulsion C. subfalcine herniation D. tonsilar hernaition E. uncle herniation

*uncle herniation* *Uncal herniations* occur when the medial aspect of the temporal lobe (uncus) herniates across the tentorium cerebelli in response to a tumor, cerebral edema caused by accident or trauma, or a large infarct. This initially compresses the oculomotor nerve and the crus cerebri in the midbrain. Oculomotor nerve lesion results in ptosis, mydriasis (dilated pupil), and lateral strabismus (eye directed inferiorly and laterally). The ptosis is due to a weak levator palpebrae superioris muscle, the mydriasis is due to impaired parasympathetic innervation of the pupil, and the lateral strabismus is due to weakness in 4 of the 6 extraocular eye muscles. Crus cerebri lesion results in contralateral hemiparesis of the extremities. This is due to the involvement of the corticospinal tract descending through the crus cerebri. As the herniation progresses, the respiratory system can be compromised with a rapid decline for the patient. In a minority of patients with uncal herniation, the midbrain is displaced into the tentorial notch on the contralateral side. This can compress the contralateral corticospinal tract leading to hemiparesis ipsilateral to the uncal herniation. This false localizing sign is called Kernohan's phenomenon. Image: Compression of midbrain by uncal herniation. Oculomotor nerve and crus cerebri are typically affected. Answer A: The most common circle of Willis aneurysm is in the anterior communicating artery, with rupture resulting in a subarachnoid hemorrhage. Patients typically present with an acute onset of a severe headache that is often described as "the worst headache of my life" along with double vision, nausea, and vomiting. Answer B: Posterior inferior cerebellar artery occlusion leads to lateral medullary syndrome, characterized by loss of pain sensation from one side of the face and the other side of the body, along with Horner syndrome, ataxia, nystagmus, and other symptoms. However, hemiparesis is not a clinical sign for lateral medullary syndrome. Answer C: Subfalcine herniation (cingulate herniation) occurs when increased intracranial pressure causes herniation of the medial aspect of the cerebral hemisphere, the cingulate gyrus, under the edge of the falx cerebri. This results in less pressure on the brainstem than other herniations but can cause abnormal posturing and coma. Subfalcine herniations can be due to cerebral edema caused by an accident or trauma. Answer D: Tonsillar herniation occurs when increased intracranial pressure in the posterior fossa displaces the cerebellar tonsils downward through the foramen magnum. This results in compression of the lower brainstem, with initial signs of headache and neck stiffness, and potentially respiratory arrest followed by cardiac arrest. Tonsillar herniations are commonly due to hydrocephalus and congenital defects such as Arnold Chiari malformations. *Bottom Line*: Uncal herniations occur when the medial aspect of the temporal lobe (uncus) herniates across the tentorium cerebelli. This initially results in ptosis, mydriasis, lateral strabismus, and contralateral hemiparesis of the extremities.

A 28-year-old male presents to his primary care physician complaining of pain in the left wrist and hand. He works as a computer programmer and notes increased symptoms at the end of the day that seem to affect digits 1-3. Symptoms have been ongoing for almost 2 years, with splints and nonsteroidal anti-inflammatory drugs providing only minimal effectiveness. He is beginning to drop things and is having difficulty opening up jars. The pain awakens him at night, and he states that he now has difficulty concentrating due to the interruptions in sleep. He has no other past medical history and takes no medications. He admits to occasional alcohol intake but denies tobacco use. Vital signs are within normal limits. Physical examination reveals mild atrophy of the thenar eminence. He reports pain when he performs the physical examination maneuver shown in the exhibit video (+ Phalen test). *What other findings would most likely be seen on his physical examination?* A. dec. sensation in the thenar eminance B. weakness of the 2nd and 3rd digit abduction (dorsal interossei) C. weakness of the 2nd and 3rd digit adduction (dorsal interossei) D. weakness of thumb adduction (adductor polliciis brevis) E. weakness of thumb flexion (flexor pollicis brevis)

*weakness of thumb flexion (flexor pollicis brevis)* This patient is most likely suffering from carpal tunnel syndrome, a condition in which the median nerve becomes entrapped under the flexor retinaculum, leading to pain, numbness, tingling, and weakness of the intrinsic hand muscles in the distribution of the median nerve. The median nerve provides motor innervation to thenar muscles that include the opponens pollicis, abductor pollicis brevis, and flexor pollicis brevis. Note: The video in the exhibit demonstrates Phalen test, which is further discussed below. Long-standing carpal tunnel syndrome may cause weakness in flexion of the thumb at the MCP joint and impairment of thumb opposition and abduction. Weakness of the first and second lumbricals leads to weakness of the first and second finger flexion at the MCP joint. Long-term impingement can cause atrophy of these muscles, which is an indication for surgical decompression. Diagnosis of carpal tunnel syndrome is made clinically. Provocative testing for carpal tunnel syndrome includes the Tinel test, Phalen test, and reverse Phalen test (aka prayer test): Tinel test: This is performed by lightly tapping on the median nerve over the wrist, causing direct irritation to the nerve. Phalen test: The patient flexes both wrists to 90° and presses the backs of the hands together, compressing the median nerve (held for 60 seconds). Reverse Phalen (prayer) test: The patient maintains both wrists at maximal extension, placing the palms together for 60 seconds. A positive test reproduces symptoms (pins and needle sensation) along the median nerve distribution that includes the median nerve territory, with involvement of the first 3 digits and the radial half of the fourth digit. Sensation to the thenar eminence is spared, as this is supplied by the palmar cutaneous nerve, a branch of the median nerve arising proximal to the carpal tunnel and, therefore, is not affected. Answer A: The thenar eminence obtains sensory innervation from the palmar branch of the median nerve. This nerve branches off the median nerve proximal to the retinaculum and does not cross through carpal tunnel; therefore, it is not affected with carpal tunnel syndrome. Patients will have decreased sensation over digit 1 but not the thenar eminence or palm. This answer choice is incorrect. Answer B: Dorsal interossei are intrinsic muscles of the hand that abduct the fingers. Similarly to the palmar interossei, these muscles are innervated by the ulnar nerve. Although the ulnar nerve is most commonly compressed at the cubital tunnel, it may also be compressed at Guyon's canal, also called the ulnar canal, which is a space on the ulnar side of the wrist. Regardless, this patient's clinical findings are most consistent with carpal tunnel syndrome, a median nerve neuropathy, making this choice incorrect. Answer C: Palmar interossei are intrinsic muscles of the hand that adduct the fingers. They are innervated by the ulnar nerve, which is most commonly compressed at the cubital tunnel (medial side of the elbow). Patients affected with cubital tunnel syndrome most often complain of paresthesia and numbness involving the ring and little fingers (4th and 5th digits). These symptoms are not consistent with what the patient is experiencing, making this answer incorrect. Answer D: Adductor pollicis brevis along with medial lumbricals, dorsal interossei, palmar interossei, and hypothenar muscles are all innervated by the ulnar nerve. By contrast, abductor pollicis brevis is one of the thenar muscles, all of which are innervated by the median nerve and assist in thumb opposition, abduction, and flexion. Carpal tunnel syndrome affects the median distribution, not ulnar, making this answer incorrect. *Bottom Line*: Carpal tunnel syndrome is the most common upper extremity compressive neuropathy, which affects the median nerve as it travels through the carpal tunnel in the wrist. Long-standing carpal tunnel syndrome may cause weakness and atrophy of the muscles innervated by the median nerve including the thenar eminence (opponens pollicis, abductor pollicis brevis, and flexor pollicis brevis) and the first and second lumbricals. *COMBANK Insight*: Remember the median-innervated hand muscles by the mnemonic *LOAF*: first and second *L*umbricals, *O*pponens pollicis, *A*bductor pollicis brevis, and *F*lexor pollicis brevis.

A 45-year-old American missionary presents to his primary care physician after a one year visit to a remote village in Africa. You learn that the patient is an agricultural engineer who helps village tribes find sources of water and build canals from adjacent rivers to water their crops. Physical examination reveals small diffuse subcutaneous nodules in the groin as well as atrophy, hyperpigmentation, and drooping of the groin skin. Additionally, vision in both eyes has decreased rapidly over the past month, and he now complains of eye itching and redness. On ophthalmic examination the patient has iridocyclitis, and you send him for emergent consultation by an ophthalmologist. *Which of the following is the most likely diagnosis?* A. Behcet's Dz B. Kala-azar C. Loasis D. Onchocerciasis E. Sarcoidosis

The patient is most likely suffering from *onchocerciasis*, which is an infection caused by Onchocerca volvulus. This parasite is transmitted by the black fly, which is found in Africa, Yemen, and parts of South America. The majority of cases are found in the continent of Africa and it is the second-leading infectious cause of blindness worldwide (after trachoma caused by Chlamydia trachomatis serotypes A-C). When a human is bitten by the black fly, the fly transmits the parasitic larvae into the bloodstream of the human. After infection, the larvae grow to adult worms within the bloodstream and lymphatics. The adults embed into the skin, forming subcutaneous nodules and bear microfilarial offspring which invade the eye and its inner chambers. Overall, these offspring cause eye pain, redness, iritis, and anterior uveitis in the patient. These microfilarial worms disseminate throughout the body, causing an allergic-type reaction and a skin condition known as onchodermatitis. This disease is also known as river blindness because the black flies live near the rivers and the native tribes realized that the individuals who went down to the rivers were the only people in the village who would eventually go blind. The treatment of choice for this disease is an antiparasitic ivermectin. Answer A: Behcet's disease is a rare autoimmune vasculitis that presents with recurrent oral ulcerations, genital ulcerations, and anterior uveitis. Answer B: Kala-azar, also known as visceral leishmaniasis, is caused by the parasite Leishmania donovani. It is transmitted by the sandfly and is commonly found in India. It causes spiking fevers, hepatosplenomegaly, and pancytopenia. The treatment of choice is sodium stibogluconate. Answer C: Loiasis is an infection with the parasite Loa loa. It can cause swelling of the skin and presence of subcutaneous worms. It infects the conjunctiva of the eye, in which worms are visible. While it does specifically affect the eye, Loa loa rarely leads to blindness. It is transmitted by Chrysops flies (including the deer fly, horse fly, and mango fly). The treatment of choice is diethylcarbamazine. Answer E: Sarcoidosis has an unknown etiology. However, it is associated with abnormal collections of chronic inflammatory cells the form granulomas. It can present as an interstitial lung disease, hilar lymphadenopathy, anterior uveitis, cardiac involvement, or systemic skin involvement. *Bottom Line*: Onchocerciasis, also known as river blindness, presents 9-12 months after being infected with the parasite by the bite of a black fly and can lead to irreversible blindness.